Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era</title><author><name sortKey="Costain, Gregory" sort="Costain, Gregory" uniqKey="Costain G" first="Gregory" last="Costain">Gregory Costain</name><affiliation><nlm:aff id="af1-tacg-5-001">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af2-tacg-5-001">Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S" last="Bassett">Anne S. Bassett</name><affiliation><nlm:aff id="af1-tacg-5-001">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af2-tacg-5-001">Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af3-tacg-5-001">Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af4-tacg-5-001">Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23144566</idno><idno type="pmc">3492098</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492098</idno><idno type="RBID">PMC:3492098</idno><idno type="doi">10.2147/TACG.S21953</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000C00</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C00</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era</title><author><name sortKey="Costain, Gregory" sort="Costain, Gregory" uniqKey="Costain G" first="Gregory" last="Costain">Gregory Costain</name><affiliation><nlm:aff id="af1-tacg-5-001">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af2-tacg-5-001">Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Bassett, Anne S" sort="Bassett, Anne S" uniqKey="Bassett A" first="Anne S" last="Bassett">Anne S. Bassett</name><affiliation><nlm:aff id="af1-tacg-5-001">Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af2-tacg-5-001">Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af3-tacg-5-001">Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="af4-tacg-5-001">Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></analytic><series><title level="j">The Application of Clinical Genetics</title><idno type="eISSN">1178-704X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression) of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Insel, Tr" uniqKey="Insel T">TR Insel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Scherer, Sw" uniqKey="Scherer S">SW Scherer</name></author><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gejman, Pv" uniqKey="Gejman P">PV Gejman</name></author><author><name sortKey="Sanders, Ar" uniqKey="Sanders A">AR Sanders</name></author><author><name sortKey="Kendler, Ks" uniqKey="Kendler K">KS Kendler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hochstenbach, R" uniqKey="Hochstenbach R">R Hochstenbach</name></author><author><name sortKey="Buizer Voskamp, Je" uniqKey="Buizer Voskamp J">JE Buizer-Voskamp</name></author><author><name sortKey="Vorstman, Ja" uniqKey="Vorstman J">JA Vorstman</name></author><author><name sortKey="Ophoff, Ra" uniqKey="Ophoff R">RA Ophoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author><author><name sortKey="Zerwas, S" uniqKey="Zerwas S">S Zerwas</name></author><author><name sortKey="Trace, Se" uniqKey="Trace S">SE Trace</name></author><author><name sortKey="Sullivan, Pf" uniqKey="Sullivan P">PF Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez Murillo, L" uniqKey="Rodriguez Murillo L">L Rodriguez-Murillo</name></author><author><name sortKey="Gogos, Ja" uniqKey="Gogos J">JA Gogos</name></author><author><name sortKey="Karayiorgou, M" uniqKey="Karayiorgou M">M Karayiorgou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ewc" uniqKey="Chow E">EWC Chow</name></author><author><name sortKey="Hodgkinson, Ka" uniqKey="Hodgkinson K">KA Hodgkinson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collier, Da" uniqKey="Collier D">DA Collier</name></author><author><name sortKey="Vassos, E" uniqKey="Vassos E">E Vassos</name></author><author><name sortKey="Holden, S" uniqKey="Holden S">S Holden</name></author><author><name sortKey="Patch, C" uniqKey="Patch C">C Patch</name></author><author><name sortKey="Mcguire, P" uniqKey="Mcguire P">P McGuire</name></author><author><name sortKey="Lewis, C" uniqKey="Lewis C">C Lewis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moreno De Luca, D" uniqKey="Moreno De Luca D">D Moreno-De-Luca</name></author><author><name sortKey="Cubells, Jf" uniqKey="Cubells J">JF Cubells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mueser, Kt" uniqKey="Mueser K">KT Mueser</name></author><author><name sortKey="Jeste, Dv" uniqKey="Jeste D">DV Jeste</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harper, Ps" uniqKey="Harper P">PS Harper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cannon, Td" uniqKey="Cannon T">TD Cannon</name></author><author><name sortKey="Kaprio, J" uniqKey="Kaprio J">J Kaprio</name></author><author><name sortKey="Lonnqvist, J" uniqKey="Lonnqvist J">J Lonnqvist</name></author><author><name sortKey="Huttunen, M" uniqKey="Huttunen M">M Huttunen</name></author><author><name sortKey="Koskenvuo, M" uniqKey="Koskenvuo M">M Koskenvuo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cardno, Ag" uniqKey="Cardno A">AG Cardno</name></author><author><name sortKey="Gottesman, Ii" uniqKey="Gottesman I">II Gottesman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kendler, Ks" uniqKey="Kendler K">KS Kendler</name></author><author><name sortKey="Diehl, Sr" uniqKey="Diehl S">SR Diehl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author><author><name sortKey="O Onovan, Mc" uniqKey="O Onovan M">MC O’Donovan</name></author><author><name sortKey="Owen, Mj" uniqKey="Owen M">MJ Owen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gottesman, Ii" uniqKey="Gottesman I">II Gottesman</name></author><author><name sortKey="Shields, J" uniqKey="Shields J">J Shields</name></author><author><name sortKey="Hanson, Dr" uniqKey="Hanson D">DR Hanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gottesman, Ii" uniqKey="Gottesman I">II Gottesman</name></author><author><name sortKey="Wolfgram, Dl" uniqKey="Wolfgram D">DL Wolfgram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kendler, Ks" uniqKey="Kendler K">KS Kendler</name></author><author><name sortKey="Gruenberg, Am" uniqKey="Gruenberg A">AM Gruenberg</name></author><author><name sortKey="Tsuang, Mt" uniqKey="Tsuang M">MT Tsuang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowing, Pa" uniqKey="Lowing P">PA Lowing</name></author><author><name sortKey="Mirsky, Af" uniqKey="Mirsky A">AF Mirsky</name></author><author><name sortKey="Pereira, R" uniqKey="Pereira R">R Pereira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moldin, So" uniqKey="Moldin S">SO Moldin</name></author><author><name sortKey="Gottesman, Ii" uniqKey="Gottesman I">II Gottesman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tienari, Pj" uniqKey="Tienari P">PJ Tienari</name></author><author><name sortKey="Wynne, Lc" uniqKey="Wynne L">LC Wynne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abdelmalik, P" uniqKey="Abdelmalik P">P AbdelMalik</name></author><author><name sortKey="Husted, J" uniqKey="Husted J">J Husted</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrne, M" uniqKey="Byrne M">M Byrne</name></author><author><name sortKey="Browne, R" uniqKey="Browne R">R Browne</name></author><author><name sortKey="Mulryan, N" uniqKey="Mulryan N">N Mulryan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henquet, C" uniqKey="Henquet C">C Henquet</name></author><author><name sortKey="Di Forti, M" uniqKey="Di Forti M">M Di Forti</name></author><author><name sortKey="Morrison, P" uniqKey="Morrison P">P Morrison</name></author><author><name sortKey="Kuepper, R" uniqKey="Kuepper R">R Kuepper</name></author><author><name sortKey="Murray, Rm" uniqKey="Murray R">RM Murray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcguffin, P" uniqKey="Mcguffin P">P McGuffin</name></author><author><name sortKey="Asherson, P" uniqKey="Asherson P">P Asherson</name></author><author><name sortKey="Owen, M" uniqKey="Owen M">M Owen</name></author><author><name sortKey="Farmer, A" uniqKey="Farmer A">A Farmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matheson, Sl" uniqKey="Matheson S">SL Matheson</name></author><author><name sortKey="Shepherd, Am" uniqKey="Shepherd A">AM Shepherd</name></author><author><name sortKey="Laurens, Kr" uniqKey="Laurens K">KR Laurens</name></author><author><name sortKey="Carr, Vj" uniqKey="Carr V">VJ Carr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moore, Th" uniqKey="Moore T">TH Moore</name></author><author><name sortKey="Zammit, S" uniqKey="Zammit S">S Zammit</name></author><author><name sortKey="Lingford Hughes, A" uniqKey="Lingford Hughes A">A Lingford-Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tienari, P" uniqKey="Tienari P">P Tienari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wahlberg, Ke" uniqKey="Wahlberg K">KE Wahlberg</name></author><author><name sortKey="Wynne, Lc" uniqKey="Wynne L">LC Wynne</name></author><author><name sortKey="Oja, H" uniqKey="Oja H">H Oja</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gottesman, Ii" uniqKey="Gottesman I">II Gottesman</name></author><author><name sortKey="Bertelsen, A" uniqKey="Bertelsen A">A Bertelsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kringlen, E" uniqKey="Kringlen E">E Kringlen</name></author><author><name sortKey="Cramer, G" uniqKey="Cramer G">G Cramer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="O Eill, S" uniqKey="O Eill S">S O’Neill</name></author><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Waterworth, Dm" uniqKey="Waterworth D">DM Waterworth</name></author><author><name sortKey="Brzustowicz, L" uniqKey="Brzustowicz L">L Brzustowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prasad, Km" uniqKey="Prasad K">KM Prasad</name></author><author><name sortKey="Talkowski, Me" uniqKey="Talkowski M">ME Talkowski</name></author><author><name sortKey="Chowdari, Kv" uniqKey="Chowdari K">KV Chowdari</name></author><author><name sortKey="Mcclain, L" uniqKey="Mcclain L">L McClain</name></author><author><name sortKey="Yolken, Rh" uniqKey="Yolken R">RH Yolken</name></author><author><name sortKey="Nimgaonkar, Vl" uniqKey="Nimgaonkar V">VL Nimgaonkar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Risch, N" uniqKey="Risch N">N Risch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Phillips, Pc" uniqKey="Phillips P">PC Phillips</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Book, Ja" uniqKey="Book J">JA Book</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penrose, Ls" uniqKey="Penrose L">LS Penrose</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcclellan, Jm" uniqKey="Mcclellan J">JM McClellan</name></author><author><name sortKey="Susser, E" uniqKey="Susser E">E Susser</name></author><author><name sortKey="King, Mc" uniqKey="King M">MC King</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Zackai, Eh" uniqKey="Zackai E">EH Zackai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shprintzen, Rj" uniqKey="Shprintzen R">RJ Shprintzen</name></author><author><name sortKey="Goldberg, R" uniqKey="Goldberg R">R Goldberg</name></author><author><name sortKey="Golding Kushner, Kj" uniqKey="Golding Kushner K">KJ Golding-Kushner</name></author><author><name sortKey="Marion, Rw" uniqKey="Marion R">RW Marion</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Devriendt, K" uniqKey="Devriendt K">K Devriendt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karayiorgou, M" uniqKey="Karayiorgou M">M Karayiorgou</name></author><author><name sortKey="Simon, Tj" uniqKey="Simon T">TJ Simon</name></author><author><name sortKey="Gogos, Ja" uniqKey="Gogos J">JA Gogos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Philip, N" uniqKey="Philip N">N Philip</name></author><author><name sortKey="Bassett, A" uniqKey="Bassett A">A Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sandrin Garcia, P" uniqKey="Sandrin Garcia P">P Sandrin-Garcia</name></author><author><name sortKey="Abramides, Dv" uniqKey="Abramides D">DV Abramides</name></author><author><name sortKey="Martelli, Lr" uniqKey="Martelli L">LR Martelli</name></author><author><name sortKey="Ramos, Es" uniqKey="Ramos E">ES Ramos</name></author><author><name sortKey="Richieri Costa, A" uniqKey="Richieri Costa A">A Richieri- Costa</name></author><author><name sortKey="Passos, Ga" uniqKey="Passos G">GA Passos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weksberg, R" uniqKey="Weksberg R">R Weksberg</name></author><author><name sortKey="Stachon, Ac" uniqKey="Stachon A">AC Stachon</name></author><author><name sortKey="Squire, Ja" uniqKey="Squire J">JA Squire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edelmann, L" uniqKey="Edelmann L">L Edelmann</name></author><author><name sortKey="Pandita, Rk" uniqKey="Pandita R">RK Pandita</name></author><author><name sortKey="Morrow, Be" uniqKey="Morrow B">BE Morrow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stankiewicz, P" uniqKey="Stankiewicz P">P Stankiewicz</name></author><author><name sortKey="Lupski, Jr" uniqKey="Lupski J">JR Lupski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Marshall, Cr" uniqKey="Marshall C">CR Marshall</name></author><author><name sortKey="Lionel, Ac" uniqKey="Lionel A">AC Lionel</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Scherer, Sw" uniqKey="Scherer S">SW Scherer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, E" uniqKey="Cohen E">E Cohen</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Weksberg, R" uniqKey="Weksberg R">R Weksberg</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Digilio, Mc" uniqKey="Digilio M">MC Digilio</name></author><author><name sortKey="Angioni, A" uniqKey="Angioni A">A Angioni</name></author><author><name sortKey="De Santis, M" uniqKey="De Santis M">M De Santis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Tonnesen, Mk" uniqKey="Tonnesen M">MK Tonnesen</name></author><author><name sortKey="Laufer Cahana, A" uniqKey="Laufer Cahana A">A Laufer-Cahana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Costain, G" uniqKey="Costain G">G Costain</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Silversides, Ck" uniqKey="Silversides C">CK Silversides</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lupski, Jr" uniqKey="Lupski J">JR Lupski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kobrynski, Lj" uniqKey="Kobrynski L">LJ Kobrynski</name></author><author><name sortKey="Sullivan, Ke" uniqKey="Sullivan K">KE Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Sullivan, Ke" uniqKey="Sullivan K">KE Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Dt" uniqKey="Miller D">DT Miller</name></author><author><name sortKey="Adam, Mp" uniqKey="Adam M">MP Adam</name></author><author><name sortKey="Aradhya, S" uniqKey="Aradhya S">S Aradhya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tokuyasu, Ta" uniqKey="Tokuyasu T">TA Tokuyasu</name></author><author><name sortKey="Cotter, Pd" uniqKey="Cotter P">PD Cotter</name></author><author><name sortKey="Segraves, R" uniqKey="Segraves R">R Segraves</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Husted, J" uniqKey="Husted J">J Husted</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cooper, Gm" uniqKey="Cooper G">GM Cooper</name></author><author><name sortKey="Coe, Bp" uniqKey="Coe B">BP Coe</name></author><author><name sortKey="Girirajan, S" uniqKey="Girirajan S">S Girirajan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Costain, G" uniqKey="Costain G">G Costain</name></author><author><name sortKey="Fung, Wl" uniqKey="Fung W">WL Fung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, Wl" uniqKey="Fung W">WL Fung</name></author><author><name sortKey="Mcevilly, R" uniqKey="Mcevilly R">R McEvilly</name></author><author><name sortKey="Fong, J" uniqKey="Fong J">J Fong</name></author><author><name sortKey="Silversides, Ck" uniqKey="Silversides C">CK Silversides</name></author><author><name sortKey="Chow, Ewc" uniqKey="Chow E">EWC Chow</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Murphy, Kc" uniqKey="Murphy K">KC Murphy</name></author><author><name sortKey="Jones, La" uniqKey="Jones L">LA Jones</name></author><author><name sortKey="Owen, Mj" uniqKey="Owen M">MJ Owen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Amelsvoort, T" uniqKey="Van Amelsvoort T">T van Amelsvoort</name></author><author><name sortKey="Henry, J" uniqKey="Henry J">J Henry</name></author><author><name sortKey="Morris, R" uniqKey="Morris R">R Morris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Abdelmalik, P" uniqKey="Abdelmalik P">P AbdelMalik</name></author><author><name sortKey="Gheorghiu, M" uniqKey="Gheorghiu M">M Gheorghiu</name></author><author><name sortKey="Husted, J" uniqKey="Husted J">J Husted</name></author><author><name sortKey="Weksberg, R" uniqKey="Weksberg R">R Weksberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Watson, M" uniqKey="Watson M">M Watson</name></author><author><name sortKey="Young, Da" uniqKey="Young D">DA Young</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stoddard, J" uniqKey="Stoddard J">J Stoddard</name></author><author><name sortKey="Niendam, T" uniqKey="Niendam T">T Niendam</name></author><author><name sortKey="Hendren, R" uniqKey="Hendren R">R Hendren</name></author><author><name sortKey="Carter, C" uniqKey="Carter C">C Carter</name></author><author><name sortKey="Simon, Tj" uniqKey="Simon T">TJ Simon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Torres Juan, L" uniqKey="Torres Juan L">L Torres-Juan</name></author><author><name sortKey="Rosell, J" uniqKey="Rosell J">J Rosell</name></author><author><name sortKey="Sanchez De La Torre, M" uniqKey="Sanchez De La Torre M">M Sanchez-de-la-Torre</name></author><author><name sortKey="Fibla, J" uniqKey="Fibla J">J Fibla</name></author><author><name sortKey="Heine Suner, D" uniqKey="Heine Suner D">D Heine-Suner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antshel, Km" uniqKey="Antshel K">KM Antshel</name></author><author><name sortKey="Fremont, W" uniqKey="Fremont W">W Fremont</name></author><author><name sortKey="Roizen, Nj" uniqKey="Roizen N">NJ Roizen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Husted, J" uniqKey="Husted J">J Husted</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Booij, J" uniqKey="Booij J">J Booij</name></author><author><name sortKey="Van Amelsvoort, T" uniqKey="Van Amelsvoort T">T van Amelsvoort</name></author><author><name sortKey="Boot, E" uniqKey="Boot E">E Boot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Smedt, B" uniqKey="De Smedt B">B De Smedt</name></author><author><name sortKey="Swillen, A" uniqKey="Swillen A">A Swillen</name></author><author><name sortKey="Verschaffel, L" uniqKey="Verschaffel L">L Verschaffel</name></author><author><name sortKey="Ghesquiere, P" uniqKey="Ghesquiere P">P Ghesquiere</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Green, T" uniqKey="Green T">T Green</name></author><author><name sortKey="Gothelf, D" uniqKey="Gothelf D">D Gothelf</name></author><author><name sortKey="Glaser, B" uniqKey="Glaser B">B Glaser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hercher, L" uniqKey="Hercher L">L Hercher</name></author><author><name sortKey="Bruenner, G" uniqKey="Bruenner G">G Bruenner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jolin, Em" uniqKey="Jolin E">EM Jolin</name></author><author><name sortKey="Weller, Ra" uniqKey="Weller R">RA Weller</name></author><author><name sortKey="Jessani, Nr" uniqKey="Jessani N">NR Jessani</name></author><author><name sortKey="Zackai, Eh" uniqKey="Zackai E">EH Zackai</name></author><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Weller, Eb" uniqKey="Weller E">EB Weller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kapadia, Rk" uniqKey="Kapadia R">RK Kapadia</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawrence, S" uniqKey="Lawrence S">S Lawrence</name></author><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Zackai, E" uniqKey="Zackai E">E Zackai</name></author><author><name sortKey="Sullivan, Ke" uniqKey="Sullivan K">KE Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Kirschner, R" uniqKey="Kirschner R">R Kirschner</name></author><author><name sortKey="Goldmuntz, E" uniqKey="Goldmuntz E">E Goldmuntz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald Mcginn, Dm" uniqKey="Mcdonald Mcginn D">DM McDonald-McGinn</name></author><author><name sortKey="Zackai, Eh" uniqKey="Zackai E">EH Zackai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oskarsdottir, S" uniqKey="Oskarsdottir S">S Oskarsdottir</name></author><author><name sortKey="Persson, C" uniqKey="Persson C">C Persson</name></author><author><name sortKey="Eriksson, Bo" uniqKey="Eriksson B">BO Eriksson</name></author><author><name sortKey="Fasth, A" uniqKey="Fasth A">A Fasth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ryan, Ak" uniqKey="Ryan A">AK Ryan</name></author><author><name sortKey="Goodship, Ja" uniqKey="Goodship J">JA Goodship</name></author><author><name sortKey="Wilson, Di" uniqKey="Wilson D">DI Wilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vantrappen, G" uniqKey="Vantrappen G">G Vantrappen</name></author><author><name sortKey="Devriendt, K" uniqKey="Devriendt K">K Devriendt</name></author><author><name sortKey="Swillen, A" uniqKey="Swillen A">A Swillen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaleski, C" uniqKey="Zaleski C">C Zaleski</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Tam, K" uniqKey="Tam K">K Tam</name></author><author><name sortKey="Shugar, Al" uniqKey="Shugar A">AL Shugar</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Mcpherson, E" uniqKey="Mcpherson E">E McPherson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Husted, J" uniqKey="Husted J">J Husted</name></author><author><name sortKey="Weksberg, R" uniqKey="Weksberg R">R Weksberg</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gothelf, D" uniqKey="Gothelf D">D Gothelf</name></author><author><name sortKey="Eliez, S" uniqKey="Eliez S">S Eliez</name></author><author><name sortKey="Thompson, T" uniqKey="Thompson T">T Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vorstman, Ja" uniqKey="Vorstman J">JA Vorstman</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Ophoff, Ra" uniqKey="Ophoff R">RA Ophoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, T" uniqKey="Guo T">T Guo</name></author><author><name sortKey="Mcdonald Mcginn, D" uniqKey="Mcdonald Mcginn D">D McDonald-McGinn</name></author><author><name sortKey="Blonska, A" uniqKey="Blonska A">A Blonska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Swaby, Ja" uniqKey="Swaby J">JA Swaby</name></author><author><name sortKey="Silversides, Ck" uniqKey="Silversides C">CK Silversides</name></author><author><name sortKey="Bekeschus, Sc" uniqKey="Bekeschus S">SC Bekeschus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Caluseriu, O" uniqKey="Caluseriu O">O Caluseriu</name></author><author><name sortKey="Weksberg, R" uniqKey="Weksberg R">R Weksberg</name></author><author><name sortKey="Young, Da" uniqKey="Young D">DA Young</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boot, E" uniqKey="Boot E">E Boot</name></author><author><name sortKey="Booij, J" uniqKey="Booij J">J Booij</name></author><author><name sortKey="Abeling, N" uniqKey="Abeling N">N Abeling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ikeda, M" uniqKey="Ikeda M">M Ikeda</name></author><author><name sortKey="Williams, N" uniqKey="Williams N">N Williams</name></author><author><name sortKey="Williams, Hj" uniqKey="Williams H">HJ Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antshel, Km" uniqKey="Antshel K">KM Antshel</name></author><author><name sortKey="Shprintzen, R" uniqKey="Shprintzen R">R Shprintzen</name></author><author><name sortKey="Fremont, W" uniqKey="Fremont W">W Fremont</name></author><author><name sortKey="Higgins, Am" uniqKey="Higgins A">AM Higgins</name></author><author><name sortKey="Faraone, Sv" uniqKey="Faraone S">SV Faraone</name></author><author><name sortKey="Kates, Wr" uniqKey="Kates W">WR Kates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gothelf, D" uniqKey="Gothelf D">D Gothelf</name></author><author><name sortKey="Feinstein, C" uniqKey="Feinstein C">C Feinstein</name></author><author><name sortKey="Thompson, T" uniqKey="Thompson T">T Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gothelf, D" uniqKey="Gothelf D">D Gothelf</name></author><author><name sortKey="Hoeft, F" uniqKey="Hoeft F">F Hoeft</name></author><author><name sortKey="Ueno, T" uniqKey="Ueno T">T Ueno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Ho, A" uniqKey="Ho A">A Ho</name></author><author><name sortKey="Wei, C" uniqKey="Wei C">C Wei</name></author><author><name sortKey="Voormolen, Eh" uniqKey="Voormolen E">EH Voormolen</name></author><author><name sortKey="Crawley, Ap" uniqKey="Crawley A">AP Crawley</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, R" uniqKey="Emsley R">R Emsley</name></author><author><name sortKey="Chiliza, B" uniqKey="Chiliza B">B Chiliza</name></author><author><name sortKey="Schoeman, R" uniqKey="Schoeman R">R Schoeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bromet, Ej" uniqKey="Bromet E">EJ Bromet</name></author><author><name sortKey="Kotov, R" uniqKey="Kotov R">R Kotov</name></author><author><name sortKey="Fochtmann, Lj" uniqKey="Fochtmann L">LJ Fochtmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Werner, S" uniqKey="Werner S">S Werner</name></author><author><name sortKey="Stawski, M" uniqKey="Stawski M">M Stawski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Badner, Ja" uniqKey="Badner J">JA Badner</name></author><author><name sortKey="Gershon, Es" uniqKey="Gershon E">ES Gershon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lewis, Cm" uniqKey="Lewis C">CM Lewis</name></author><author><name sortKey="Levinson, Df" uniqKey="Levinson D">DF Levinson</name></author><author><name sortKey="Wise, Lh" uniqKey="Wise L">LH Wise</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, My" uniqKey="Ng M">MY Ng</name></author><author><name sortKey="Levinson, Df" uniqKey="Levinson D">DF Levinson</name></author><author><name sortKey="Faraone, Sv" uniqKey="Faraone S">SV Faraone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Owen, Mj" uniqKey="Owen M">MJ Owen</name></author><author><name sortKey="Williams, Nm" uniqKey="Williams N">NM Williams</name></author><author><name sortKey="O Onovan, Mc" uniqKey="O Onovan M">MC O’Donovan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waterwort, Dm" uniqKey="Waterwort D">DM Waterwort</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blouin, Jl" uniqKey="Blouin J">JL Blouin</name></author><author><name sortKey="Dombroski, Ba" uniqKey="Dombroski B">BA Dombroski</name></author><author><name sortKey="Nath, Sk" uniqKey="Nath S">SK Nath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author><author><name sortKey="Honer, Wg" uniqKey="Honer W">WG Honer</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author><author><name sortKey="Hodgkinson, Ka" uniqKey="Hodgkinson K">KA Hodgkinson</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Honer, Wg" uniqKey="Honer W">WG Honer</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekelund, J" uniqKey="Ekelund J">J Ekelund</name></author><author><name sortKey="Hovatta, I" uniqKey="Hovatta I">I Hovatta</name></author><author><name sortKey="Parker, A" uniqKey="Parker A">A Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gurling, Hm" uniqKey="Gurling H">HM Gurling</name></author><author><name sortKey="Kalsi, G" uniqKey="Kalsi G">G Kalsi</name></author><author><name sortKey="Brynjolfson, J" uniqKey="Brynjolfson J">J Brynjolfson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holmans, Pa" uniqKey="Holmans P">PA Holmans</name></author><author><name sortKey="Riley, B" uniqKey="Riley B">B Riley</name></author><author><name sortKey="Pulver, Ae" uniqKey="Pulver A">AE Pulver</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Mw" uniqKey="Lin M">MW Lin</name></author><author><name sortKey="Sham, P" uniqKey="Sham P">P Sham</name></author><author><name sortKey="Hwu, Hg" uniqKey="Hwu H">HG Hwu</name></author><author><name sortKey="Collier, D" uniqKey="Collier D">D Collier</name></author><author><name sortKey="Murray, R" uniqKey="Murray R">R Murray</name></author><author><name sortKey="Powell, Jf" uniqKey="Powell J">JF Powell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, Sh" uniqKey="Shaw S">SH Shaw</name></author><author><name sortKey="Kelly, M" uniqKey="Kelly M">M Kelly</name></author><author><name sortKey="Smith, Ab" uniqKey="Smith A">AB Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stefansson, H" uniqKey="Stefansson H">H Stefansson</name></author><author><name sortKey="Sigurdsson, E" uniqKey="Sigurdsson E">E Sigurdsson</name></author><author><name sortKey="Steinthorsdottir, V" uniqKey="Steinthorsdottir V">V Steinthorsdottir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Straub, Re" uniqKey="Straub R">RE Straub</name></author><author><name sortKey="Maclean, Cj" uniqKey="Maclean C">CJ MacLean</name></author><author><name sortKey="O Eill, Fa" uniqKey="O Eill F">FA O’Neill</name></author><author><name sortKey="Walsh, D" uniqKey="Walsh D">D Walsh</name></author><author><name sortKey="Kendler, Ks" uniqKey="Kendler K">KS Kendler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vieland, Vj" uniqKey="Vieland V">VJ Vieland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faraone, Sv" uniqKey="Faraone S">SV Faraone</name></author><author><name sortKey="Hwu, Hg" uniqKey="Hwu H">HG Hwu</name></author><author><name sortKey="Liu, Cm" uniqKey="Liu C">CM Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goes, Fs" uniqKey="Goes F">FS Goes</name></author><author><name sortKey="Zandi, Pp" uniqKey="Zandi P">PP Zandi</name></author><author><name sortKey="Miao, K" uniqKey="Miao K">K Miao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suarez, Bk" uniqKey="Suarez B">BK Suarez</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J Duan</name></author><author><name sortKey="Sanders, Ar" uniqKey="Sanders A">AR Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wratten, Ns" uniqKey="Wratten N">NS Wratten</name></author><author><name sortKey="Memoli, H" uniqKey="Memoli H">H Memoli</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gershon, Es" uniqKey="Gershon E">ES Gershon</name></author><author><name sortKey="Alliey Rodriguez, N" uniqKey="Alliey Rodriguez N">N Alliey-Rodriguez</name></author><author><name sortKey="Liu, C" uniqKey="Liu C">C Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Athanasiu, L" uniqKey="Athanasiu L">L Athanasiu</name></author><author><name sortKey="Mattingsdal, M" uniqKey="Mattingsdal M">M Mattingsdal</name></author><author><name sortKey="Kahler, Ak" uniqKey="Kahler A">AK Kahler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lencz, T" uniqKey="Lencz T">T Lencz</name></author><author><name sortKey="Morgan, Tv" uniqKey="Morgan T">TV Morgan</name></author><author><name sortKey="Athanasiou, M" uniqKey="Athanasiou M">M Athanasiou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Need, Ac" uniqKey="Need A">AC Need</name></author><author><name sortKey="Ge, D" uniqKey="Ge D">D Ge</name></author><author><name sortKey="Weale, Me" uniqKey="Weale M">ME Weale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schanze, D" uniqKey="Schanze D">D Schanze</name></author><author><name sortKey="Ekici, Ab" uniqKey="Ekici A">AB Ekici</name></author><author><name sortKey="Gawlik, M" uniqKey="Gawlik M">M Gawlik</name></author><author><name sortKey="Pfuhlmann, B" uniqKey="Pfuhlmann B">B Pfuhlmann</name></author><author><name sortKey="Reis, A" uniqKey="Reis A">A Reis</name></author><author><name sortKey="Stober, G" uniqKey="Stober G">G Stober</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sullivan, Pf" uniqKey="Sullivan P">PF Sullivan</name></author><author><name sortKey="Lin, D" uniqKey="Lin D">D Lin</name></author><author><name sortKey="Tzeng, Jy" uniqKey="Tzeng J">JY Tzeng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Onovan, Mc" uniqKey="O Onovan M">MC O’Donovan</name></author><author><name sortKey="Craddock, N" uniqKey="Craddock N">N Craddock</name></author><author><name sortKey="Norton, N" uniqKey="Norton N">N Norton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Purcell, Sm" uniqKey="Purcell S">SM Purcell</name></author><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name></author><author><name sortKey="Stone, Jl" uniqKey="Stone J">JL Stone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rietschel, M" uniqKey="Rietschel M">M Rietschel</name></author><author><name sortKey="Mattheisen, M" uniqKey="Mattheisen M">M Mattheisen</name></author><author><name sortKey="Degenhardt, F" uniqKey="Degenhardt F">F Degenhardt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ripke, S" uniqKey="Ripke S">S Ripke</name></author><author><name sortKey="Sanders, Ar" uniqKey="Sanders A">AR Sanders</name></author><author><name sortKey="Kendler, Ks" uniqKey="Kendler K">KS Kendler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, J" uniqKey="Shi J">J Shi</name></author><author><name sortKey="Levinson, Df" uniqKey="Levinson D">DF Levinson</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J Duan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stefansson, H" uniqKey="Stefansson H">H Stefansson</name></author><author><name sortKey="Ophoff, Ra" uniqKey="Ophoff R">RA Ophoff</name></author><author><name sortKey="Steinberg, S" uniqKey="Steinberg S">S Steinberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamada, K" uniqKey="Yamada K">K Yamada</name></author><author><name sortKey="Iwayama, Y" uniqKey="Iwayama Y">Y Iwayama</name></author><author><name sortKey="Hattori, E" uniqKey="Hattori E">E Hattori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yue, Wh" uniqKey="Yue W">WH Yue</name></author><author><name sortKey="Wang, Hf" uniqKey="Wang H">HF Wang</name></author><author><name sortKey="Sun, Ld" uniqKey="Sun L">LD Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crowe, Rr" uniqKey="Crowe R">RR Crowe</name></author><author><name sortKey="Thompson, Js" uniqKey="Thompson J">JS Thompson</name></author><author><name sortKey="Flink, R" uniqKey="Flink R">R Flink</name></author><author><name sortKey="Weinberger, B" uniqKey="Weinberger B">B Weinberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eberhard, G" uniqKey="Eberhard G">G Eberhard</name></author><author><name sortKey="Franzen, G" uniqKey="Franzen G">G Franzen</name></author><author><name sortKey="Low, B" uniqKey="Low B">B Low</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name></author><author><name sortKey="Xu, Q" uniqKey="Xu Q">Q Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steinberg, S" uniqKey="Steinberg S">S Steinberg</name></author><author><name sortKey="De Jong, S" uniqKey="De Jong S">S de Jong</name></author><author><name sortKey="Andreassen, Oa" uniqKey="Andreassen O">OA Andreassen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Ks" uniqKey="Wang K">KS Wang</name></author><author><name sortKey="Liu, Xf" uniqKey="Liu X">XF Liu</name></author><author><name sortKey="Aragam, N" uniqKey="Aragam N">N Aragam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Williams, Hj" uniqKey="Williams H">HJ Williams</name></author><author><name sortKey="Norton, N" uniqKey="Norton N">N Norton</name></author><author><name sortKey="Dwyer, S" uniqKey="Dwyer S">S Dwyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glessner, Jt" uniqKey="Glessner J">JT Glessner</name></author><author><name sortKey="Reilly, Mp" uniqKey="Reilly M">MP Reilly</name></author><author><name sortKey="Kim, Ce" uniqKey="Kim C">CE Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arranz, Mj" uniqKey="Arranz M">MJ Arranz</name></author><author><name sortKey="Rivera, M" uniqKey="Rivera M">M Rivera</name></author><author><name sortKey="Munro, Jc" uniqKey="Munro J">JC Munro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cacabelos, R" uniqKey="Cacabelos R">R Cacabelos</name></author><author><name sortKey="Hashimoto, R" uniqKey="Hashimoto R">R Hashimoto</name></author><author><name sortKey="Takeda, M" uniqKey="Takeda M">M Takeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hodgkinson, Ka" uniqKey="Hodgkinson K">KA Hodgkinson</name></author><author><name sortKey="Murphy, J" uniqKey="Murphy J">J Murphy</name></author><author><name sortKey="O Eill, S" uniqKey="O Eill S">S O’Neill</name></author><author><name sortKey="Brzustowicz, L" uniqKey="Brzustowicz L">L Brzustowicz</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Allen, Nc" uniqKey="Allen N">NC Allen</name></author><author><name sortKey="Bagade, S" uniqKey="Bagade S">S Bagade</name></author><author><name sortKey="Mcqueen, Mb" uniqKey="Mcqueen M">MB McQueen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Girard, Sl" uniqKey="Girard S">SL Girard</name></author><author><name sortKey="Gauthier, J" uniqKey="Gauthier J">J Gauthier</name></author><author><name sortKey="Noreau, A" uniqKey="Noreau A">A Noreau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, B" uniqKey="Xu B">B Xu</name></author><author><name sortKey="Roos, Jl" uniqKey="Roos J">JL Roos</name></author><author><name sortKey="Dexheimer, P" uniqKey="Dexheimer P">P Dexheimer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cook, Eh" uniqKey="Cook E">EH Cook</name></author><author><name sortKey="Scherer, Sw" uniqKey="Scherer S">SW Scherer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iafrate, Aj" uniqKey="Iafrate A">AJ Iafrate</name></author><author><name sortKey="Feuk, L" uniqKey="Feuk L">L Feuk</name></author><author><name sortKey="Rivera, Mn" uniqKey="Rivera M">MN Rivera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, C" uniqKey="Lee C">C Lee</name></author><author><name sortKey="Scherer, Sw" uniqKey="Scherer S">SW Scherer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Redon, R" uniqKey="Redon R">R Redon</name></author><author><name sortKey="Ishikawa, S" uniqKey="Ishikawa S">S Ishikawa</name></author><author><name sortKey="Fitch, Kr" uniqKey="Fitch K">KR Fitch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sebat, J" uniqKey="Sebat J">J Sebat</name></author><author><name sortKey="Lakshmi, B" uniqKey="Lakshmi B">B Lakshmi</name></author><author><name sortKey="Troge, J" uniqKey="Troge J">J Troge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ingason, A" uniqKey="Ingason A">A Ingason</name></author><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author><author><name sortKey="Giegling, I" uniqKey="Giegling I">I Giegling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grozeva, D" uniqKey="Grozeva D">D Grozeva</name></author><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author><author><name sortKey="Ivanov, D" uniqKey="Ivanov D">D Ivanov</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author><author><name sortKey="Grozeva, D" uniqKey="Grozeva D">D Grozeva</name></author><author><name sortKey="Norton, N" uniqKey="Norton N">N Norton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author><author><name sortKey="Pocklington, Aj" uniqKey="Pocklington A">AJ Pocklington</name></author><author><name sortKey="Holmans, P" uniqKey="Holmans P">P Holmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magri, C" uniqKey="Magri C">C Magri</name></author><author><name sortKey="Sacchetti, E" uniqKey="Sacchetti E">E Sacchetti</name></author><author><name sortKey="Traversa, M" uniqKey="Traversa M">M Traversa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melhem, N" uniqKey="Melhem N">N Melhem</name></author><author><name sortKey="Middleton, F" uniqKey="Middleton F">F Middleton</name></author><author><name sortKey="Mcfadden, K" uniqKey="Mcfadden K">K McFadden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stefansson, H" uniqKey="Stefansson H">H Stefansson</name></author><author><name sortKey="Rujescu, D" uniqKey="Rujescu D">D Rujescu</name></author><author><name sortKey="Cichon, S" uniqKey="Cichon S">S Cichon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moreno De Luca, D" uniqKey="Moreno De Luca D">D Moreno-De-Luca</name></author><author><name sortKey="Mulle, Jg" uniqKey="Mulle J">JG Mulle</name></author><author><name sortKey="Kaminsky, Eb" uniqKey="Kaminsky E">EB Kaminsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levinson, Df" uniqKey="Levinson D">DF Levinson</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J Duan</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S Oh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ingason, A" uniqKey="Ingason A">A Ingason</name></author><author><name sortKey="Rujescu, D" uniqKey="Rujescu D">D Rujescu</name></author><author><name sortKey="Cichon, S" uniqKey="Cichon S">S Cichon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunetti Pierri, N" uniqKey="Brunetti Pierri N">N Brunetti-Pierri</name></author><author><name sortKey="Berg, Js" uniqKey="Berg J">JS Berg</name></author><author><name sortKey="Scaglia, F" uniqKey="Scaglia F">F Scaglia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doornbos, M" uniqKey="Doornbos M">M Doornbos</name></author><author><name sortKey="Sikkema Raddatz, B" uniqKey="Sikkema Raddatz B">B Sikkema-Raddatz</name></author><author><name sortKey="Ruijvenkamp, Ca" uniqKey="Ruijvenkamp C">CA Ruijvenkamp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greenway, Sc" uniqKey="Greenway S">SC Greenway</name></author><author><name sortKey="Pereira, Ac" uniqKey="Pereira A">AC Pereira</name></author><author><name sortKey="Lin, Jc" uniqKey="Lin J">JC Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hannes, Fd" uniqKey="Hannes F">FD Hannes</name></author><author><name sortKey="Sharp, Aj" uniqKey="Sharp A">AJ Sharp</name></author><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harvard, C" uniqKey="Harvard C">C Harvard</name></author><author><name sortKey="Strong, E" uniqKey="Strong E">E Strong</name></author><author><name sortKey="Mercier, E" uniqKey="Mercier E">E Mercier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Kovel, Cg" uniqKey="De Kovel C">CG de Kovel</name></author><author><name sortKey="Trucks, H" uniqKey="Trucks H">H Trucks</name></author><author><name sortKey="Helbig, I" uniqKey="Helbig I">I Helbig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Clauin, S" uniqKey="Clauin S">S Clauin</name></author><author><name sortKey="Sharp, Aj" uniqKey="Sharp A">AJ Sharp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Sharp, Aj" uniqKey="Sharp A">AJ Sharp</name></author><author><name sortKey="Baker, C" uniqKey="Baker C">C Baker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Cooper, Gm" uniqKey="Cooper G">GM Cooper</name></author><author><name sortKey="Zerr, T" uniqKey="Zerr T">T Zerr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagamani, Sc" uniqKey="Nagamani S">SC Nagamani</name></author><author><name sortKey="Erez, A" uniqKey="Erez A">A Erez</name></author><author><name sortKey="Shen, J" uniqKey="Shen J">J Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ullmann, R" uniqKey="Ullmann R">R Ullmann</name></author><author><name sortKey="Turner, G" uniqKey="Turner G">G Turner</name></author><author><name sortKey="Kirchhoff, M" uniqKey="Kirchhoff M">M Kirchhoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Williams, Nm" uniqKey="Williams N">NM Williams</name></author><author><name sortKey="Zaharieva, I" uniqKey="Zaharieva I">I Zaharieva</name></author><author><name sortKey="Martin, A" uniqKey="Martin A">A Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Horowitz, A" uniqKey="Horowitz A">A Horowitz</name></author><author><name sortKey="Shifman, S" uniqKey="Shifman S">S Shifman</name></author><author><name sortKey="Rivlin, N" uniqKey="Rivlin N">N Rivlin</name></author><author><name sortKey="Pisante, A" uniqKey="Pisante A">A Pisante</name></author><author><name sortKey="Darvasi, A" uniqKey="Darvasi A">A Darvasi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walsh, T" uniqKey="Walsh T">T Walsh</name></author><author><name sortKey="Mcclellan, Jm" uniqKey="Mcclellan J">JM McClellan</name></author><author><name sortKey="Mccarthy, Se" uniqKey="Mccarthy S">SE McCarthy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sporn, A" uniqKey="Sporn A">A Sporn</name></author><author><name sortKey="Addington, A" uniqKey="Addington A">A Addington</name></author><author><name sortKey="Reiss, Al" uniqKey="Reiss A">AL Reiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rapoport, Jl" uniqKey="Rapoport J">JL Rapoport</name></author><author><name sortKey="Addington, Am" uniqKey="Addington A">AM Addington</name></author><author><name sortKey="Frangou, S" uniqKey="Frangou S">S Frangou</name></author><author><name sortKey="Psych, Mr" uniqKey="Psych M">MR Psych</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Girirajan, S" uniqKey="Girirajan S">S Girirajan</name></author><author><name sortKey="Eichler, Ee" uniqKey="Eichler E">EE Eichler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Costain, G" uniqKey="Costain G">G Costain</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Ray, Pn" uniqKey="Ray P">PN Ray</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hodgkinson, K" uniqKey="Hodgkinson K">K Hodgkinson</name></author><author><name sortKey="Pullman, D" uniqKey="Pullman D">D Pullman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Piggins, Hd" uniqKey="Piggins H">HD Piggins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Green, Ed" uniqKey="Green E">ED Green</name></author><author><name sortKey="Guyer, Ms" uniqKey="Guyer M">MS Guyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scherer, Sw" uniqKey="Scherer S">SW Scherer</name></author><author><name sortKey="Dawson, G" uniqKey="Dawson G">G Dawson</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Fa" uniqKey="Miller F">FA Miller</name></author><author><name sortKey="Hayeems, Rz" uniqKey="Hayeems R">RZ Hayeems</name></author><author><name sortKey="Bytautas, Jp" uniqKey="Bytautas J">JP Bytautas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author><author><name sortKey="Bury, A" uniqKey="Bury A">A Bury</name></author><author><name sortKey="Hodgkinson, Ka" uniqKey="Hodgkinson K">KA Hodgkinson</name></author><author><name sortKey="Honer, Wg" uniqKey="Honer W">WG Honer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bundy, H" uniqKey="Bundy H">H Bundy</name></author><author><name sortKey="Stahl, D" uniqKey="Stahl D">D Stahl</name></author><author><name sortKey="Maccabe, Jh" uniqKey="Maccabe J">JH MacCabe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitchell, Pb" uniqKey="Mitchell P">PB Mitchell</name></author><author><name sortKey="Meiser, B" uniqKey="Meiser B">B Meiser</name></author><author><name sortKey="Wilde, A" uniqKey="Wilde A">A Wilde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsuang, Dw" uniqKey="Tsuang D">DW Tsuang</name></author><author><name sortKey="Faraone, Sv" uniqKey="Faraone S">SV Faraone</name></author><author><name sortKey="Tsuang, Mt" uniqKey="Tsuang M">MT Tsuang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feret, H" uniqKey="Feret H">H Feret</name></author><author><name sortKey="Conway, L" uniqKey="Conway L">L Conway</name></author><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Monaco, Lc" uniqKey="Monaco L">LC Monaco</name></author><author><name sortKey="Conway, L" uniqKey="Conway L">L Conway</name></author><author><name sortKey="Valverde, K" uniqKey="Valverde K">K Valverde</name></author><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Finucane, B" uniqKey="Finucane B">B Finucane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, Mr" uniqKey="Taylor M">MR Taylor</name></author><author><name sortKey="Edwards, Jg" uniqKey="Edwards J">JG Edwards</name></author><author><name sortKey="Ku, L" uniqKey="Ku L">L Ku</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Farwig, K" uniqKey="Farwig K">K Farwig</name></author><author><name sortKey="Harmon, Ag" uniqKey="Harmon A">AG Harmon</name></author><author><name sortKey="Fontana, Km" uniqKey="Fontana K">KM Fontana</name></author><author><name sortKey="Mervis, Cb" uniqKey="Mervis C">CB Mervis</name></author><author><name sortKey="Morris, Ca" uniqKey="Morris C">CA Morris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, C" uniqKey="Lee C">C Lee</name></author><author><name sortKey="Iafrate, Aj" uniqKey="Iafrate A">AJ Iafrate</name></author><author><name sortKey="Brothman, Ar" uniqKey="Brothman A">AR Brothman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author><author><name sortKey="Peay, Hl" uniqKey="Peay H">HL Peay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peay, Hl" uniqKey="Peay H">HL Peay</name></author><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpson, Sa" uniqKey="Simpson S">SA Simpson</name></author><author><name sortKey="Besson, J" uniqKey="Besson J">J Besson</name></author><author><name sortKey="Alexander, D" uniqKey="Alexander D">D Alexander</name></author><author><name sortKey="Allan, K" uniqKey="Allan K">K Allan</name></author><author><name sortKey="Johnston, Aw" uniqKey="Johnston A">AW Johnston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tyler, A" uniqKey="Tyler A">A Tyler</name></author><author><name sortKey="Morris, M" uniqKey="Morris M">M Morris</name></author><author><name sortKey="Lazarou, L" uniqKey="Lazarou L">L Lazarou</name></author><author><name sortKey="Meredith, L" uniqKey="Meredith L">L Meredith</name></author><author><name sortKey="Myring, J" uniqKey="Myring J">J Myring</name></author><author><name sortKey="Harper, P" uniqKey="Harper P">P Harper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, B" uniqKey="Xu B">B Xu</name></author><author><name sortKey="Woodroffe, A" uniqKey="Woodroffe A">A Woodroffe</name></author><author><name sortKey="Rodriguez Murillo, L" uniqKey="Rodriguez Murillo L">L Rodriguez-Murillo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Chalabi, A" uniqKey="Al Chalabi A">A Al-Chalabi</name></author><author><name sortKey="Lewis, Cm" uniqKey="Lewis C">CM Lewis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name></author><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shulman, Jm" uniqKey="Shulman J">JM Shulman</name></author><author><name sortKey="De Jager, Pl" uniqKey="De Jager P">PL De Jager</name></author><author><name sortKey="Feany, Mb" uniqKey="Feany M">MB Feany</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guttmacher, Ae" uniqKey="Guttmacher A">AE Guttmacher</name></author><author><name sortKey="Collins, Fs" uniqKey="Collins F">FS Collins</name></author><author><name sortKey="Carmona, Rh" uniqKey="Carmona R">RH Carmona</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Papadimitriou, Gn" uniqKey="Papadimitriou G">GN Papadimitriou</name></author><author><name sortKey="Dikeos, Dg" uniqKey="Dikeos D">DG Dikeos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reveley, A" uniqKey="Reveley A">A Reveley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsuang, Mt" uniqKey="Tsuang M">MT Tsuang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hunter, Mj" uniqKey="Hunter M">MJ Hunter</name></author><author><name sortKey="Hippman, C" uniqKey="Hippman C">C Hippman</name></author><author><name sortKey="Honer, Wg" uniqKey="Honer W">WG Honer</name></author><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lyus, Vl" uniqKey="Lyus V">VL Lyus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Austin, Jc" uniqKey="Austin J">JC Austin</name></author><author><name sortKey="Honer, Wg" uniqKey="Honer W">WG Honer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Torrey, Ef" uniqKey="Torrey E">EF Torrey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bruder, Ce" uniqKey="Bruder C">CE Bruder</name></author><author><name sortKey="Piotrowski, A" uniqKey="Piotrowski A">A Piotrowski</name></author><author><name sortKey="Gijsbers, Aa" uniqKey="Gijsbers A">AA Gijsbers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dempster, El" uniqKey="Dempster E">EL Dempster</name></author><author><name sortKey="Pidsley, R" uniqKey="Pidsley R">R Pidsley</name></author><author><name sortKey="Schalkwyk, Lc" uniqKey="Schalkwyk L">LC Schalkwyk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kato, T" uniqKey="Kato T">T Kato</name></author><author><name sortKey="Iwamoto, K" uniqKey="Iwamoto K">K Iwamoto</name></author><author><name sortKey="Kakiuchi, C" uniqKey="Kakiuchi C">C Kakiuchi</name></author><author><name sortKey="Kuratomi, G" uniqKey="Kuratomi G">G Kuratomi</name></author><author><name sortKey="Okazaki, Y" uniqKey="Okazaki Y">Y Okazaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maiti, S" uniqKey="Maiti S">S Maiti</name></author><author><name sortKey="Kumar, Kh" uniqKey="Kumar K">KH Kumar</name></author><author><name sortKey="Castellani, Ca" uniqKey="Castellani C">CA Castellani</name></author><author><name sortKey="O Eilly, R" uniqKey="O Eilly R">R O’Reilly</name></author><author><name sortKey="Singh, Sm" uniqKey="Singh S">SM Singh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Husted, Ja" uniqKey="Husted J">JA Husted</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author><author><name sortKey="Chow, Ew" uniqKey="Chow E">EW Chow</name></author><author><name sortKey="Brzustowicz, Lm" uniqKey="Brzustowicz L">LM Brzustowicz</name></author><author><name sortKey="Bassett, As" uniqKey="Bassett A">AS Bassett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Os, J" uniqKey="Van Os J">J van Os</name></author><author><name sortKey="Kenis, G" uniqKey="Kenis G">G Kenis</name></author><author><name sortKey="Rutten, Bp" uniqKey="Rutten B">BP Rutten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurnit, Dm" uniqKey="Kurnit D">DM Kurnit</name></author><author><name sortKey="Layton, Wm" uniqKey="Layton W">WM Layton</name></author><author><name sortKey="Matthysse, S" uniqKey="Matthysse S">S Matthysse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruvinsky, A" uniqKey="Ruvinsky A">A Ruvinsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lichtenstein, P" uniqKey="Lichtenstein P">P Lichtenstein</name></author><author><name sortKey="Bjork, C" uniqKey="Bjork C">C Bjork</name></author><author><name sortKey="Hultman, Cm" uniqKey="Hultman C">CM Hultman</name></author><author><name sortKey="Scolnick, E" uniqKey="Scolnick E">E Scolnick</name></author><author><name sortKey="Sklar, P" uniqKey="Sklar P">P Sklar</name></author><author><name sortKey="Sullivan, Pf" uniqKey="Sullivan P">PF Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slatkin, M" uniqKey="Slatkin M">M Slatkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name></author><author><name sortKey="Goddard, Me" uniqKey="Goddard M">ME Goddard</name></author><author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slatkin, M" uniqKey="Slatkin M">M Slatkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drmanac, R" uniqKey="Drmanac R">R Drmanac</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greenspan, Si" uniqKey="Greenspan S">SI Greenspan</name></author><author><name sortKey="Brazelton, Tb" uniqKey="Brazelton T">TB Brazelton</name></author><author><name sortKey="Cordero, J" uniqKey="Cordero J">J Cordero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miles, Jh" uniqKey="Miles J">JH Miles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kjeldsen, Mj" uniqKey="Kjeldsen M">MJ Kjeldsen</name></author><author><name sortKey="Kyvik, Ko" uniqKey="Kyvik K">KO Kyvik</name></author><author><name sortKey="Christensen, K" uniqKey="Christensen K">K Christensen</name></author><author><name sortKey="Friis, Ml" uniqKey="Friis M">ML Friis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulley, Jc" uniqKey="Mulley J">JC Mulley</name></author><author><name sortKey="Dibbens, Lm" uniqKey="Dibbens L">LM Dibbens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pal, Dk" uniqKey="Pal D">DK Pal</name></author><author><name sortKey="Pong, Aw" uniqKey="Pong A">AW Pong</name></author><author><name sortKey="Chung, Wk" uniqKey="Chung W">WK Chung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poduri, A" uniqKey="Poduri A">A Poduri</name></author><author><name sortKey="Lowenstein, D" uniqKey="Lowenstein D">D Lowenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, K" uniqKey="Sharma K">K Sharma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Do, Cb" uniqKey="Do C">CB Do</name></author><author><name sortKey="Tung, Jy" uniqKey="Tung J">JY Tung</name></author><author><name sortKey="Dorfman, E" uniqKey="Dorfman E">E Dorfman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elbaz, A" uniqKey="Elbaz A">A Elbaz</name></author><author><name sortKey="Bower, Jh" uniqKey="Bower J">JH Bower</name></author><author><name sortKey="Maraganore, Dm" uniqKey="Maraganore D">DM Maraganore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schulte, C" uniqKey="Schulte C">C Schulte</name></author><author><name sortKey="Gasser, T" uniqKey="Gasser T">T Gasser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toft, M" uniqKey="Toft M">M Toft</name></author><author><name sortKey="Ross, Oa" uniqKey="Ross O">OA Ross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ballard, C" uniqKey="Ballard C">C Ballard</name></author><author><name sortKey="Gauthier, S" uniqKey="Gauthier S">S Gauthier</name></author><author><name sortKey="Corbett, A" uniqKey="Corbett A">A Corbett</name></author><author><name sortKey="Brayne, C" uniqKey="Brayne C">C Brayne</name></author><author><name sortKey="Aarsland, D" uniqKey="Aarsland D">D Aarsland</name></author><author><name sortKey="Jones, E" uniqKey="Jones E">E Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, L" uniqKey="Bertram L">L Bertram</name></author><author><name sortKey="Lill, Cm" uniqKey="Lill C">CM Lill</name></author><author><name sortKey="Tanzi, Re" uniqKey="Tanzi R">RE Tanzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gatz, M" uniqKey="Gatz M">M Gatz</name></author><author><name sortKey="Reynolds, Ca" uniqKey="Reynolds C">CA Reynolds</name></author><author><name sortKey="Fratiglioni, L" uniqKey="Fratiglioni L">L Fratiglioni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldman, Js" uniqKey="Goldman J">JS Goldman</name></author><author><name sortKey="Hahn, Se" uniqKey="Hahn S">SE Hahn</name></author><author><name sortKey="Catania, Jw" uniqKey="Catania J">JW Catania</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coulter, Me" uniqKey="Coulter M">ME Coulter</name></author><author><name sortKey="Miller, Dt" uniqKey="Miller D">DT Miller</name></author><author><name sortKey="Harris, Dj" uniqKey="Harris D">DJ Harris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basel Vanagaite, L" uniqKey="Basel Vanagaite L">L Basel-Vanagaite</name></author><author><name sortKey="Goldberg Stern, H" uniqKey="Goldberg Stern H">H Goldberg-Stern</name></author><author><name sortKey="Mimouni Bloch, A" uniqKey="Mimouni Bloch A">A Mimouni-Bloch</name></author><author><name sortKey="Shkalim, V" uniqKey="Shkalim V">V Shkalim</name></author><author><name sortKey="Bohm, D" uniqKey="Bohm D">D Bohm</name></author><author><name sortKey="Kohlhase, J" uniqKey="Kohlhase J">J Kohlhase</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunet, A" uniqKey="Brunet A">A Brunet</name></author><author><name sortKey="Armengol, L" uniqKey="Armengol L">L Armengol</name></author><author><name sortKey="Heine, D" uniqKey="Heine D">D Heine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Christiansen, J" uniqKey="Christiansen J">J Christiansen</name></author><author><name sortKey="Dyck, Jd" uniqKey="Dyck J">JD Dyck</name></author><author><name sortKey="Elyas, Bg" uniqKey="Elyas B">BG Elyas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ikeda, M" uniqKey="Ikeda M">M Ikeda</name></author><author><name sortKey="Aleksic, B" uniqKey="Aleksic B">B Aleksic</name></author><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sahoo, T" uniqKey="Sahoo T">T Sahoo</name></author><author><name sortKey="Theisen, A" uniqKey="Theisen A">A Theisen</name></author><author><name sortKey="Rosenfeld, Ja" uniqKey="Rosenfeld J">JA Rosenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vu, Th" uniqKey="Vu T">TH Vu</name></author><author><name sortKey="Coccaro, Ef" uniqKey="Coccaro E">EF Coccaro</name></author><author><name sortKey="Eichler, Ee" uniqKey="Eichler E">EE Eichler</name></author><author><name sortKey="Girirajan, S" uniqKey="Girirajan S">S Girirajan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ballif, Bc" uniqKey="Ballif B">BC Ballif</name></author><author><name sortKey="Theisen, A" uniqKey="Theisen A">A Theisen</name></author><author><name sortKey="Coppinger, J" uniqKey="Coppinger J">J Coppinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clayton Smith, J" uniqKey="Clayton Smith J">J Clayton-Smith</name></author><author><name sortKey="Giblin, C" uniqKey="Giblin C">C Giblin</name></author><author><name sortKey="Smith, Ra" uniqKey="Smith R">RA Smith</name></author><author><name sortKey="Dunn, C" uniqKey="Dunn C">C Dunn</name></author><author><name sortKey="Willatt, L" uniqKey="Willatt L">L Willatt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Digilio, Mc" uniqKey="Digilio M">MC Digilio</name></author><author><name sortKey="Bernardini, L" uniqKey="Bernardini L">L Bernardini</name></author><author><name sortKey="Mingarelli, R" uniqKey="Mingarelli R">R Mingarelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulle, Jg" uniqKey="Mulle J">JG Mulle</name></author><author><name sortKey="Dodd, Af" uniqKey="Dodd A">AF Dodd</name></author><author><name sortKey="Mcgrath, Ja" uniqKey="Mcgrath J">JA McGrath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quintero Rivera, F" uniqKey="Quintero Rivera F">F Quintero-Rivera</name></author><author><name sortKey="Sharifi Hannauer, P" uniqKey="Sharifi Hannauer P">P Sharifi-Hannauer</name></author><author><name sortKey="Martinez Agosto, Ja" uniqKey="Martinez Agosto J">JA Martinez-Agosto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vacic, V" uniqKey="Vacic V">V Vacic</name></author><author><name sortKey="Mccarthy, S" uniqKey="Mccarthy S">S McCarthy</name></author><author><name sortKey="Malhotra, D" uniqKey="Malhotra D">D Malhotra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Willatt, L" uniqKey="Willatt L">L Willatt</name></author><author><name sortKey="Cox, J" uniqKey="Cox J">J Cox</name></author><author><name sortKey="Barber, J" uniqKey="Barber J">J Barber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Browne, Ce" uniqKey="Browne C">CE Browne</name></author><author><name sortKey="Dennis, Nr" uniqKey="Dennis N">NR Dennis</name></author><author><name sortKey="Maher, E" uniqKey="Maher E">E Maher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chamberlain, Sj" uniqKey="Chamberlain S">SJ Chamberlain</name></author><author><name sortKey="Lalande, M" uniqKey="Lalande M">M Lalande</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cook, Eh" uniqKey="Cook E">EH Cook</name></author><author><name sortKey="Lindgren, V" uniqKey="Lindgren V">V Lindgren</name></author><author><name sortKey="Leventhal, Bl" uniqKey="Leventhal B">BL Leventhal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gurrieri, F" uniqKey="Gurrieri F">F Gurrieri</name></author><author><name sortKey="Battaglia, A" uniqKey="Battaglia A">A Battaglia</name></author><author><name sortKey="Torrisi, L" uniqKey="Torrisi L">L Torrisi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hogart, A" uniqKey="Hogart A">A Hogart</name></author><author><name sortKey="Wu, D" uniqKey="Wu D">D Wu</name></author><author><name sortKey="Lasalle, Jm" uniqKey="Lasalle J">JM LaSalle</name></author><author><name sortKey="Schanen, Nc" uniqKey="Schanen N">NC Schanen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Michelson, M" uniqKey="Michelson M">M Michelson</name></author><author><name sortKey="Eden, A" uniqKey="Eden A">A Eden</name></author><author><name sortKey="Vinkler, C" uniqKey="Vinkler C">C Vinkler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, Ja" uniqKey="Thomas J">JA Thomas</name></author><author><name sortKey="Johnson, J" uniqKey="Johnson J">J Johnson</name></author><author><name sortKey="Peterson Kraai, Tl" uniqKey="Peterson Kraai T">TL Peterson Kraai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben Shachar, S" uniqKey="Ben Shachar S">S Ben-Shachar</name></author><author><name sortKey="Lanpher, B" uniqKey="Lanpher B">B Lanpher</name></author><author><name sortKey="German, Jr" uniqKey="German J">JR German</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Bon, Bw" uniqKey="Van Bon B">BW van Bon</name></author><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Menten, B" uniqKey="Menten B">B Menten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cubells, Jf" uniqKey="Cubells J">JF Cubells</name></author><author><name sortKey="Deoreo, Eh" uniqKey="Deoreo E">EH Deoreo</name></author><author><name sortKey="Harvey, Pd" uniqKey="Harvey P">PD Harvey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dibbens, Lm" uniqKey="Dibbens L">LM Dibbens</name></author><author><name sortKey="Mullen, S" uniqKey="Mullen S">S Mullen</name></author><author><name sortKey="Helbig, I" uniqKey="Helbig I">I Helbig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Helbig, I" uniqKey="Helbig I">I Helbig</name></author><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Sharp, Aj" uniqKey="Sharp A">AJ Sharp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masurel Paulet, A" uniqKey="Masurel Paulet A">A Masurel-Paulet</name></author><author><name sortKey="Andrieux, J" uniqKey="Andrieux J">J Andrieux</name></author><author><name sortKey="Callier, P" uniqKey="Callier P">P Callier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Dt" uniqKey="Miller D">DT Miller</name></author><author><name sortKey="Shen, Y" uniqKey="Shen Y">Y Shen</name></author><author><name sortKey="Weiss, La" uniqKey="Weiss L">LA Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pagnamenta, At" uniqKey="Pagnamenta A">AT Pagnamenta</name></author><author><name sortKey="Wing, K" uniqKey="Wing K">K Wing</name></author><author><name sortKey="Sadighi Akha, E" uniqKey="Sadighi Akha E">E Sadighi Akha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharp, Aj" uniqKey="Sharp A">AJ Sharp</name></author><author><name sortKey="Mefford, Hc" uniqKey="Mefford H">HC Mefford</name></author><author><name sortKey="Li, K" uniqKey="Li K">K Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shinawi, M" uniqKey="Shinawi M">M Shinawi</name></author><author><name sortKey="Schaaf, Cp" uniqKey="Schaaf C">CP Schaaf</name></author><author><name sortKey="Bhatt, Ss" uniqKey="Bhatt S">SS Bhatt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bedoyan, Jk" uniqKey="Bedoyan J">JK Bedoyan</name></author><author><name sortKey="Kumar, Ra" uniqKey="Kumar R">RA Kumar</name></author><author><name sortKey="Sudi, J" uniqKey="Sudi J">J Sudi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fernandez, Ba" uniqKey="Fernandez B">BA Fernandez</name></author><author><name sortKey="Roberts, W" uniqKey="Roberts W">W Roberts</name></author><author><name sortKey="Chung, B" uniqKey="Chung B">B Chung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lionel, Ac" uniqKey="Lionel A">AC Lionel</name></author><author><name sortKey="Crosbie, J" uniqKey="Crosbie J">J Crosbie</name></author><author><name sortKey="Barbosa, N" uniqKey="Barbosa N">N Barbosa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccarthy, Se" uniqKey="Mccarthy S">SE McCarthy</name></author><author><name sortKey="Makarov, V" uniqKey="Makarov V">V Makarov</name></author><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marshall, Cr" uniqKey="Marshall C">CR Marshall</name></author><author><name sortKey="Noor, A" uniqKey="Noor A">A Noor</name></author><author><name sortKey="Vincent, Jb" uniqKey="Vincent J">JB Vincent</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosenfeld, Ja" uniqKey="Rosenfeld J">JA Rosenfeld</name></author><author><name sortKey="Coppinger, J" uniqKey="Coppinger J">J Coppinger</name></author><author><name sortKey="Bejjani, Ba" uniqKey="Bejjani B">BA Bejjani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schaaf, Cp" uniqKey="Schaaf C">CP Schaaf</name></author><author><name sortKey="Goin Kochel, Rp" uniqKey="Goin Kochel R">RP Goin-Kochel</name></author><author><name sortKey="Nowell, Kp" uniqKey="Nowell K">KP Nowell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shen, Y" uniqKey="Shen Y">Y Shen</name></author><author><name sortKey="Dies, Ka" uniqKey="Dies K">KA Dies</name></author><author><name sortKey="Holm, Ia" uniqKey="Holm I">IA Holm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shinawi, M" uniqKey="Shinawi M">M Shinawi</name></author><author><name sortKey="Liu, P" uniqKey="Liu P">P Liu</name></author><author><name sortKey="Kang, Sh" uniqKey="Kang S">SH Kang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, La" uniqKey="Weiss L">LA Weiss</name></author><author><name sortKey="Shen, Y" uniqKey="Shen Y">Y Shen</name></author><author><name sortKey="Korn, Jm" uniqKey="Korn J">JM Korn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodship, J" uniqKey="Goodship J">J Goodship</name></author><author><name sortKey="Cross, I" uniqKey="Cross I">I Cross</name></author><author><name sortKey="Liling, J" uniqKey="Liling J">J LiLing</name></author><author><name sortKey="Wren, C" uniqKey="Wren C">C Wren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rees, E" uniqKey="Rees E">E Rees</name></author><author><name sortKey="Moskvina, V" uniqKey="Moskvina V">V Moskvina</name></author><author><name sortKey="Owen, Mj" uniqKey="Owen M">MJ Owen</name></author><author><name sortKey="O Onovan, Mc" uniqKey="O Onovan M">MC O’Donovan</name></author><author><name sortKey="Kirov, G" uniqKey="Kirov G">G Kirov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vassos, E" uniqKey="Vassos E">E Vassos</name></author><author><name sortKey="Collier, Da" uniqKey="Collier D">DA Collier</name></author><author><name sortKey="Holden, S" uniqKey="Holden S">S Holden</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Appl Clin Genet</journal-id><journal-id journal-id-type="iso-abbrev">Appl Clin Genet</journal-id><journal-title-group><journal-title>The Application of Clinical Genetics</journal-title></journal-title-group><issn pub-type="epub">1178-704X</issn><publisher><publisher-name>Dove Medical Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23144566</article-id><article-id pub-id-type="pmc">3492098</article-id><article-id pub-id-type="doi">10.2147/TACG.S21953</article-id><article-id pub-id-type="publisher-id">tacg-5-001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Costain</surname><given-names>Gregory</given-names></name><xref ref-type="aff" rid="af1-tacg-5-001">1</xref><xref ref-type="aff" rid="af2-tacg-5-001">2</xref></contrib><contrib contrib-type="author"><name><surname>Bassett</surname><given-names>Anne S</given-names></name><xref ref-type="aff" rid="af1-tacg-5-001">1</xref><xref ref-type="aff" rid="af2-tacg-5-001">2</xref><xref ref-type="aff" rid="af3-tacg-5-001">3</xref><xref ref-type="aff" rid="af4-tacg-5-001">4</xref><xref ref-type="corresp" rid="c1-tacg-5-001"></xref></contrib></contrib-group><aff id="af1-tacg-5-001"><label>1</label>Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada</aff><aff id="af2-tacg-5-001"><label>2</label>Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada</aff><aff id="af3-tacg-5-001"><label>3</label>Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, Toronto, Ontario, Canada</aff><aff id="af4-tacg-5-001"><label>4</label>Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada</aff><author-notes><corresp id="c1-tacg-5-001">Correspondence: Anne S Bassett, Centre for Addiction and Mental Health, 33 Russell Street, Room 1100, Toronto, Ontario, Canada M5S 2S1, Tel +1 416 535 8501 ext 2731, Fax +1 416 535 7199, Email <email>anne.bassett@utoronto.ca</email></corresp></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>21</day><month>2</month><year>2012</year></pub-date><volume>5</volume><fpage>1</fpage><lpage>18</lpage><permissions><copyright-statement>© 2012 Costain and Bassett, publisher and licensee Dove Medical Press Ltd.</copyright-statement><copyright-year>2012</copyright-year><license><license-p>This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression) of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.</p></abstract><kwd-group><kwd>schizophrenia</kwd><kwd>genetics</kwd><kwd>22q11 deletion syndrome</kwd><kwd>copy number variation</kwd><kwd>genetic counseling</kwd><kwd>genetic predisposition to disease</kwd></kwd-group></article-meta></front><body><sec><title>Introduction</title><p>Schizophrenia is arguably one of humankind’s most severe diseases.<xref ref-type="bibr" rid="b1-tacg-5-001">1</xref>,<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref> Driven by new genetic technologies and advances in molecular medicine, recently there has been concrete progress in understanding some of the specific genetic origins of this complex psychiatric illness, summarized in several recent reviews.<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref>–<xref ref-type="bibr" rid="b8-tacg-5-001">8</xref> There has, however, been little focus on how we might practically apply the findings.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>–<xref ref-type="bibr" rid="b11-tacg-5-001">11</xref> In this review, we critically appraise recent developments in terms of immediate clinical utility. We use the well-established association of schizophrenia with microdeletion 22q11.2 as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.</p><sec><title>Clinical features of schizophrenia<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b12-tacg-5-001">12</xref></title><p>Schizophrenia is a common psychiatric illness that typically involves lifelong but treatable changes in thinking, behavior, and emotions. It has a lifetime morbid risk of approximately 1%. The principal symptoms are psychotic in nature: delusions (false beliefs), hallucinations (false perceptions), and thought disorder (disorganization of thought processes). In addition to these “positive” symptoms, there are also “negative” symptoms of blunted affect (reduced emotional expression), poverty of speech, anhedonia (reduced ability to feel pleasure), and amotivation, as well as disorganization of behavior and emotions. Depression, anxiety, irritability, agitation, sleep disturbance, and cognitive impairments, including changes in attention, memory, insight, and judgment, are also common. Onset of schizophrenia occurs most commonly in early adulthood from 17 to 30 years of age, but can arise in childhood (in <1% of cases) through to the elderly age range. The diagnosis of schizophrenia is a clinical diagnosis, based on course of illness as well as cross-sectional symptoms. Diagnostic reliability is high when standard diagnostic criteria are combined with a direct examination and thorough history, including information from the patient, relatives, and others, to differentiate schizophrenia from other psychotic disorders. As with most neuropsychiatric disorders, there are no characteristic neuropathological findings (<xref ref-type="table" rid="t1-tacg-5-001">Table 1</xref>), which, coupled with the absence of any diagnostic tests and substantial clinical heterogeneity (variable signs and symptoms), emphasizes the importance of detailed expert phenotyping (cf “shallow phenotyping”).<xref ref-type="bibr" rid="b13-tacg-5-001">13</xref></p></sec><sec><title>Genetic epidemiology of schizophrenia</title><p>Psychiatric genetics has historically focused in large part on the study of schizophrenia and its epidemiology.<xref ref-type="bibr" rid="b14-tacg-5-001">14</xref> It is well-established that the heritability of schizophrenia is >80%,<xref ref-type="bibr" rid="b15-tacg-5-001">15</xref>–<xref ref-type="bibr" rid="b17-tacg-5-001">17</xref> amongst the highest known for complex genetic disorders.<xref ref-type="bibr" rid="b18-tacg-5-001">18</xref> Consistent evidence from family, twin, and adoption studies over the past century strongly indicates that predisposition is largely genetically determined (MIM #181500).<xref ref-type="bibr" rid="b19-tacg-5-001">19</xref>–<xref ref-type="bibr" rid="b24-tacg-5-001">24</xref> Nongenetic factors, for example, marijuana use and hypoxiamediated factors like birth complications or childhood head injury, increase risk for schizophrenia only modestly.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b25-tacg-5-001">25</xref>–<xref ref-type="bibr" rid="b32-tacg-5-001">32</xref> Studies of schizophrenia in twins<xref ref-type="bibr" rid="b33-tacg-5-001">33</xref>,<xref ref-type="bibr" rid="b34-tacg-5-001">34</xref> support reduced penetrance (genetic variants that do not express in every carrier as disease) and variable expression (variants that express as different diseases in different carriers),<xref ref-type="bibr" rid="b35-tacg-5-001">35</xref>,<xref ref-type="bibr" rid="b36-tacg-5-001">36</xref> which is common to most human genetic diseases. As for most diseases, there is also substantial evidence for genetic heterogeneity and probably allelic heterogeneity.<xref ref-type="bibr" rid="b18-tacg-5-001">18</xref>,<xref ref-type="bibr" rid="b36-tacg-5-001">36</xref> Gene– gene interaction (epistasis) is likely in schizophrenia<xref ref-type="bibr" rid="b37-tacg-5-001">37</xref>,<xref ref-type="bibr" rid="b38-tacg-5-001">38</xref> and indeed is ubiquitous in nature.<xref ref-type="bibr" rid="b39-tacg-5-001">39</xref> Molecular evidence for early predictions of spontaneous (de novo) mutations in schizophrenia,<xref ref-type="bibr" rid="b40-tacg-5-001">40</xref>,<xref ref-type="bibr" rid="b41-tacg-5-001">41</xref> recently reframed as the “common disease – rare alleles” model,<xref ref-type="bibr" rid="b42-tacg-5-001">42</xref> adds to the complex genetic picture. Thus, it is not surprising, in hindsight, that classic Mendelian inheritance patterns are very rarely observed in schizophrenia, and that elucidation of causal genetic factors has been so challenging. Researchers have remained undeterred, because of the myriad possible benefits for patients, families, and clinicians that could result from an improved understanding of the genetic etiology of schizophrenia (<xref ref-type="table" rid="t2-tacg-5-001">Table 2</xref>).</p></sec></sec><sec><title>22q11.2 deletion syndrome</title><p>To date, 22q11.2 deletion syndrome (22q11.2DS; previously DiGeorge syndrome and velocardiofacial syndrome) is the only established genetic subtype of schizophrenia of proven clinical relevance.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b43-tacg-5-001">43</xref> The association of 22q11.2DS with schizophrenia followed soon after the discovery in the early 1990s that the 22q11.2 deletion was the underlying molecular anomaly unifying several, seemingly distinct, clinical syndromes first described in the 1960s and 1970s.<xref ref-type="bibr" rid="b44-tacg-5-001">44</xref>,<xref ref-type="bibr" rid="b45-tacg-5-001">45</xref> Many of the features suggested above with respect to the genetic epidemiology of schizophrenia, including spontaneous mutations, reduced penetrance, and variable expressivity, are found in 22q11.2DS.</p><sec><title>Molecular origins and epidemiology</title><p>22q11.2DS is associated with a hemizygous microdeletion on chromosome 22q11.2 of variable length (typically 3 Mb) and, in some cases, variable position within this region.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b46-tacg-5-001">46</xref> There is no apparent critical region at this locus for any major phenotype, including schizophrenia.<xref ref-type="bibr" rid="b47-tacg-5-001">47</xref>–<xref ref-type="bibr" rid="b50-tacg-5-001">50</xref> Most deletions are flanked by segmental duplications<xref ref-type="bibr" rid="b51-tacg-5-001">51</xref> and occur as de novo mutations mediated by nonallelic homologous recombination.<xref ref-type="bibr" rid="b46-tacg-5-001">46</xref>,<xref ref-type="bibr" rid="b52-tacg-5-001">52</xref> Only 5%–10% of cases have been found to be inherited from transmitting parents,<xref ref-type="bibr" rid="b53-tacg-5-001">53</xref>–<xref ref-type="bibr" rid="b56-tacg-5-001">56</xref> most frequently mothers with mild neuropsychiatric phenotypes.<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref> Nevertheless, 22q11.2DS is the most common genomic disorder<xref ref-type="bibr" rid="b58-tacg-5-001">58</xref> in humans, with an oft-cited estimated prevalence in the general population of 1 in 3000–4000 live births that is likely to be an underestimate.<xref ref-type="bibr" rid="b59-tacg-5-001">59</xref>,<xref ref-type="bibr" rid="b60-tacg-5-001">60</xref> Fluorescence in situ hybridization using a standard 22q11.2 probe (D22S75 or TUPLE1) has been used since 1992 to detect most deletions in this region,<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> but is now being superseded by clinical microarrays that should increase diagnostic yield.<xref ref-type="bibr" rid="b46-tacg-5-001">46</xref>,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref>,<xref ref-type="bibr" rid="b62-tacg-5-001">62</xref> Several lines of evidence support the generally pathogenic nature of 22q11.2 deletions and the high penetrance of observable phenotypes,<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b63-tacg-5-001">63</xref>,<xref ref-type="bibr" rid="b64-tacg-5-001">64</xref> so that no distinction is typically made between individuals with 22q11.2 deletions and individuals with 22q11.2DS.</p></sec><sec><title>Association with schizophrenia</title><p>Several studies have confirmed that 22q11.2DS accounts for approximately 1% of all cases of schizophrenia (see Bassett et al<xref ref-type="bibr" rid="b65-tacg-5-001">65</xref> and references therein). Conversely, an estimated 22.5% of adults with 22q11.2DS develop schizophrenia<xref ref-type="bibr" rid="b66-tacg-5-001">66</xref> or a related psychotic disorder.<xref ref-type="bibr" rid="b67-tacg-5-001">67</xref> In other words, a 22q11.2 deletion is a variant of large effect, associated with a greater than 20-fold increase in risk for schizophrenia.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> The clinical expression of the schizophrenic illness is essentially indistinguishable from that found in the general population with respect to prodrome, age at onset, presentation, cognitive profile (except for lower mean IQ), and, according to limited data available, response to treatment.<xref ref-type="bibr" rid="b43-tacg-5-001">43</xref>,<xref ref-type="bibr" rid="b66-tacg-5-001">66</xref>–<xref ref-type="bibr" rid="b71-tacg-5-001">71</xref> Thus 22q11.2DS represents the best available specific genetic model of schizophrenia, with minimized genetic heterogeneity and substantial evidence this is a representative form of this illness.<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref> Empirical evidence for a strong negative selective pressure<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref> and high rate of recombination at the 22q11.2 locus<xref ref-type="bibr" rid="b72-tacg-5-001">72</xref> is consistent with the common disease – rare variant model for schizophrenia.<xref ref-type="bibr" rid="b42-tacg-5-001">42</xref></p></sec><sec><title>Clinical relevance</title><p>For patients with schizophrenia, a clinician today should be armed with a high index of suspicion for 22q11.2DS and/or consistently use established clinical screening criteria to detect features suggesting this genetic diagnosis, such as dysmorphic facies, a nasal voice, congenital anomalies, and/or learning difficulties.<xref ref-type="bibr" rid="b65-tacg-5-001">65</xref>,<xref ref-type="bibr" rid="b73-tacg-5-001">73</xref> This would prompt a comprehensive diagnostic assessment, including developmental, medical, and family history, and a physical examination by a clinician experienced in genetic syndromes and dysmorphology.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> Genetic testing would follow if sufficient features were present to support a clinical diagnosis of 22q11.2DS<xref ref-type="bibr" rid="b73-tacg-5-001">73</xref> and should proceed in all patients with comorbid mental retardation and/or multiple congenital anomalies.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref></p><p>In a patient with schizophrenia, detection of a 22q11.2 deletion is clinically relevant.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> Consensus clinical practice guidelines<xref ref-type="bibr" rid="b46-tacg-5-001">46</xref> now exist that detail opportunities for anticipatory care and optimizing medical management of associated features, and for genetic counseling that can be informed by extensive (and rapidly expanding) knowledge of pathogenesis, recurrence risk, and lifelong expression, natural history, and clinical outcomes.<xref ref-type="bibr" rid="b54-tacg-5-001">54</xref>,<xref ref-type="bibr" rid="b56-tacg-5-001">56</xref>,<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref>,<xref ref-type="bibr" rid="b63-tacg-5-001">63</xref>,<xref ref-type="bibr" rid="b66-tacg-5-001">66</xref>,<xref ref-type="bibr" rid="b67-tacg-5-001">67</xref>,<xref ref-type="bibr" rid="b70-tacg-5-001">70</xref>,<xref ref-type="bibr" rid="b74-tacg-5-001">74</xref>–<xref ref-type="bibr" rid="b88-tacg-5-001">88</xref> Careful attention to the commonly accompanying endocrine and neurological features in particular may be helpful in the psychiatric management of patients with 22q11.2DS.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b63-tacg-5-001">63</xref> As is common in patients with schizophrenia, the psychiatrist may be the only physician the patient sees regularly and may therefore be expected to provide primary care for accompanying medical conditions, and/or have the responsibility for arranging appropriate investigations and follow-up.</p><p>For patients already diagnosed with 22q11.2DS, what are the potential implications of knowing about the risk for schizophrenia prior to first onset of psychosis? As for schizophrenia in the general population,<xref ref-type="bibr" rid="b29-tacg-5-001">29</xref> there is little evidence for any additional environmental factor(s) affecting risk of psychosis in 22q11.2DS.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b89-tacg-5-001">89</xref> Avoiding substance use, particularly early marijuana use, and lifelong general health measures such as good nutrition, and physical and mental exercise, may decrease risk to some extent.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> Common genetic modifiers of some effect may exist,<xref ref-type="bibr" rid="b90-tacg-5-001">90</xref>,<xref ref-type="bibr" rid="b91-tacg-5-001">91</xref> as for the congenital cardiac phenotype,<xref ref-type="bibr" rid="b92-tacg-5-001">92</xref>,<xref ref-type="bibr" rid="b93-tacg-5-001">93</xref> but have not been convincingly demonstrated<xref ref-type="bibr" rid="b67-tacg-5-001">67</xref>,<xref ref-type="bibr" rid="b94-tacg-5-001">94</xref>–<xref ref-type="bibr" rid="b96-tacg-5-001">96</xref> (see Philip and Bassett<xref ref-type="bibr" rid="b48-tacg-5-001">48</xref> for more details), and additional copy number variation/variants (CNV) do not seem to play a major role in expression of schizophrenia.<xref ref-type="bibr" rid="b53-tacg-5-001">53</xref> Prospective<xref ref-type="bibr" rid="b97-tacg-5-001">97</xref>–<xref ref-type="bibr" rid="b99-tacg-5-001">99</xref> and retrospective<xref ref-type="bibr" rid="b68-tacg-5-001">68</xref>,<xref ref-type="bibr" rid="b70-tacg-5-001">70</xref>,<xref ref-type="bibr" rid="b100-tacg-5-001">100</xref> research is ongoing to identify specific neurocognitive and neuroimaging predictors of future psychotic symptoms, as none are yet known. The greatest potential benefit of early diagnosis of a 22q11.2 deletion would likely be to facilitate the recognition of the early stages of schizophrenia or another psychiatric illness, and promptly seeking expert help in diagnosis and effective treatment.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b78-tacg-5-001">78</xref> Limiting the duration of untreated psychiatric illness is associated with better prognosis.<xref ref-type="bibr" rid="b101-tacg-5-001">101</xref> Psychosis in an adolescent or young adult with 22q11.2DS should also be easier to diagnostically classify as schizophrenia in its early stages because of the significant association between these two elements,<xref ref-type="bibr" rid="b102-tacg-5-001">102</xref> despite the potential additional diagnostic complexities that could be posed by comorbid mental retardation.<xref ref-type="bibr" rid="b103-tacg-5-001">103</xref></p></sec></sec><sec><title>Schizophrenia in the molecular age</title><p>Foreshadowed by the association with 22q11.2 deletions, there is further emerging evidence that multiple rare variants contribute significantly to the genetic vulnerability for schizophrenia. Other select genomic disorders caused by rare, recurring CNV represent emerging genetic subtypes of schizophrenia of growing clinical importance (<xref ref-type="table" rid="t3-tacg-5-001">Table 3</xref>). This encouraging progress comes after several decades of genome-wide and targeted molecular studies, representing essential, though largely unfruitful, tests of standard genetic hypotheses usually involving common variants at the level of nucleotide sequence (eg, single nucleotide polymorphisms [SNPs]) and DNA structure (eg, copy number polymorphisms [CNPs]). In retrospect, these studies were driven by genetically naïve expectations for schizophrenia. These included that there would exist (1) a single major locus, (2) common genetic variants of large effect, and (3) variants specific to schizophrenia (ie, not frequently associated with other conditions).</p><sec><title>Genome-wide linkage and association studies</title><sec><title>Associations with schizophrenia</title><p>Initially, several genome-wide linkage studies of multiply affected families identified regions where candidate genes for schizophrenia are likely to be. Some of these loci have been replicated and/or supported by meta-analyses,<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b18-tacg-5-001">18</xref>,<xref ref-type="bibr" rid="b104-tacg-5-001">104</xref>–<xref ref-type="bibr" rid="b108-tacg-5-001">108</xref> including 1q21-q23, 6p22, 8p21, and 13q32-q34.<xref ref-type="bibr" rid="b109-tacg-5-001">109</xref>–<xref ref-type="bibr" rid="b118-tacg-5-001">118</xref> As expected,<xref ref-type="bibr" rid="b119-tacg-5-001">119</xref> however, there are also negative studies of all loci.<xref ref-type="bibr" rid="b18-tacg-5-001">18</xref>,<xref ref-type="bibr" rid="b120-tacg-5-001">120</xref>–<xref ref-type="bibr" rid="b122-tacg-5-001">122</xref> Despite a few highly significant findings that have led, for example, to identification of functional SNPs in candidate genes,<xref ref-type="bibr" rid="b123-tacg-5-001">123</xref> one of the most important collective contributions of these studies has been the confirmation that there is no unifying single gene mutation for familial forms of schizophrenia.</p><p>In addition, there have now been several large-scale, case-control genome-wide association studies (GWAS) of schizophrenia using SNP-based microarray technology. Overall, this strategy, based on studying common SNPs, has proven to be relatively ineffective for the study of complex neuropsychiatric diseases, compared with the relative successes for auto immune diseases like diabetes and inflammatory bowel disease.<xref ref-type="bibr" rid="b124-tacg-5-001">124</xref> Some of these GWAS failed to find significant evidence of association and/or have not replicated weak associations.<xref ref-type="bibr" rid="b125-tacg-5-001">125</xref>–<xref ref-type="bibr" rid="b129-tacg-5-001">129</xref> Others have reported common sequence variants of very small effect, including several in the human leukocyte antigen (HLA) region (6p).<xref ref-type="bibr" rid="b130-tacg-5-001">130</xref>–<xref ref-type="bibr" rid="b137-tacg-5-001">137</xref> The latter findings recall early studies of protein-based HLA polymorphisms.<xref ref-type="bibr" rid="b138-tacg-5-001">138</xref>,<xref ref-type="bibr" rid="b139-tacg-5-001">139</xref> Meta-analysis using GWAS data from thousands of individuals with schizophrenia has revealed a few weak-effect associations, in the <italic>ZNF804A</italic> gene.<xref ref-type="bibr" rid="b140-tacg-5-001">140</xref>–<xref ref-type="bibr" rid="b143-tacg-5-001">143</xref> GWAS of common structural variants such as CNPs, while fewer in number, have yielded comparable findings of nominal effect.<xref ref-type="bibr" rid="b127-tacg-5-001">127</xref>,<xref ref-type="bibr" rid="b144-tacg-5-001">144</xref></p><p>GWAS using common SNPs and data on drug dosages and treatment response in schizophrenia (ie, pharmacogenomics studies) are reviewed elsewhere.<xref ref-type="bibr" rid="b145-tacg-5-001">145</xref>,<xref ref-type="bibr" rid="b146-tacg-5-001">146</xref> These show modest results similar to those for diagnosis of schizophrenia, and broad clinical applications still represent more a dream than a reality; the family history with respect to treatment response remains arguably the best predictor of treatment efficacy and side effects.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref> Findings from thousands of targeted candidate gene association studies of schizophrenia using individual SNPs (and, occasionally, specific rare sequence variants), catalogued online in the SzGene database<xref ref-type="bibr" rid="b148-tacg-5-001">148</xref> (<ext-link ext-link-type="uri" xlink:href="www.szgene.org">www.szgene.org</ext-link>) and the database of Genotypes and Phenotypes (<ext-link ext-link-type="uri" xlink:href="www.ncbi.nlm.nih.gov/gap">www.ncbi.nlm.nih.gov/gap</ext-link>), are either negative altogether or sporadically positive without replication and/or positive but with modest effect size. None are associated with a relative risk for schizophrenia anything approaching that of the ɛ4 variant of the APOE gene relative risk for Alzheimer disease (<xref ref-type="table" rid="t1-tacg-5-001">Table 1</xref>).<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> Taken together, the GWAS and targeted association study results conclusively indicate there are no common genetic variants of large effect for schizophrenia.</p></sec><sec><title>Clinical relevance</title><p>Although linkage approaches and GWAS of common variants have yielded a collection of several dozen candidate genes, the individual effect sizes of associated variants are modest. Mutation testing in these genes has no role in the clinic at this time. Larger and larger sample sizes have ensured that variants of smaller and smaller effect may be detected. Importantly, a GWAS design lacks the power to detect rare sequence variants of large effect, and it is rare variants that may collectively play a major role in the etiology of schizophrenia.<xref ref-type="bibr" rid="b124-tacg-5-001">124</xref> While preliminary findings from the first whole exome sequencing studies in schizophrenia are solely in the realm of scientific discovery at this time, they provide evidence in support of a de novo mutational paradigm at the sequence level.<xref ref-type="bibr" rid="b149-tacg-5-001">149</xref>,<xref ref-type="bibr" rid="b150-tacg-5-001">150</xref> In time, these studies may provide clinically relevant findings. However, the most notable evidence today for clinically important rare genetic variants in schizophrenia comes from studies of CNV – that is, structural genomics.</p></sec></sec><sec><title>Rare copy number variation and emerging genetic subtypes</title><p>The discovery that there is substantial structural genomic variation in the human genome that contributes to both normal variation and to susceptibility for disease is one of the major scientific advances in recent years.<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref>,<xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>,<xref ref-type="bibr" rid="b151-tacg-5-001">151</xref>–<xref ref-type="bibr" rid="b155-tacg-5-001">155</xref> Consistent with early reports of the association of schizophrenia with rare microscopically visible chromosomal abnormalities<xref ref-type="bibr" rid="b156-tacg-5-001">156</xref> and the established association with 22q11.2 deletions,<xref ref-type="bibr" rid="b43-tacg-5-001">43</xref>,<xref ref-type="bibr" rid="b66-tacg-5-001">66</xref>,<xref ref-type="bibr" rid="b67-tacg-5-001">67</xref>,<xref ref-type="bibr" rid="b69-tacg-5-001">69</xref> there is now substantial evidence for the importance of diverse rare structural variants in causing schizophrenia.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> These structural variants are mainly comprised of specific examples of large (eg, >500 kb) CNV that are consistently enriched in schizophrenia samples, and absent or extremely uncommon (ie, “rare”) in control populations.</p><sec><title>Associations with schizophrenia</title><p>Following the discovery of 22q11.2 deletions in schizophrenia, the next tier of large, rare CNV findings includes a set of emerging genetic subtypes of schizophrenia (<xref ref-type="table" rid="t3-tacg-5-001">Table 3</xref>).<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> In contrast to 22q11.2DS, the epidemiology and basic genetic parameters such as penetrance and expression remain uncertain for these genomic disorders, and there has been little to no study of the dosage-sensitive genes that may cause the associated phenotypes.<xref ref-type="bibr" rid="b64-tacg-5-001">64</xref> Collectively, however, this second tier of CNV may be as or more common in schizophrenia than 22q11.2 deletions.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> Those variants identified to date include large (>500 kb), rare, recurring (flanked by segmental duplications), hemizygous losses (deletions) and gains (duplications) at several loci (<xref ref-type="table" rid="t3-tacg-5-001">Table 3</xref>). All involve numerous genes and are consistently identified in large-scale case-control CNV studies of schizophrenia, albeit each individually at apparently low prevalence. A recent review has suggested pooled odds ratios for schizophrenia of 8 or higher for four of these five genomic disorders,<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> and for 15q11-q13 duplications of maternal origin, an initial report based on four cases suggested an odds ratio for schizophrenia of 7.3.<xref ref-type="bibr" rid="b157-tacg-5-001">157</xref> As with 22q11.2 deletions,<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> these rare structural variants may be expressed as other psychiatric illnesses and/or developmental conditions, such as autism spectrum disorders (ASDs) and epilepsy (<xref ref-type="table" rid="t3-tacg-5-001">Table 3</xref>). On the other hand, the few studies of rare CNV in bipolar disorder indicate little overlap of these forms of schizophrenia with this major mood disorder.<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref>,<xref ref-type="bibr" rid="b158-tacg-5-001">158</xref> This would be consistent with the historical clinical separation of schizophrenia and bipolar disorder based on presentation, course, and outcome, and the perhaps less “neurodevelopmental” nature of bipolar disorder. The variability of expression of 22q11.2 deletions and these other rare structural variants is shining new light on schizophrenia and on the genetically related spectrum of neuropsychiatric disorders.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> There are also other potential susceptibility factors for schizophrenia of likely smaller effect (<xref ref-type="table" rid="t4-tacg-5-001">Table 4</xref>),<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> such as hemizygous deletions at 15q11.2<xref ref-type="bibr" rid="b159-tacg-5-001">159</xref>–<xref ref-type="bibr" rid="b164-tacg-5-001">164</xref> and 17q12,<xref ref-type="bibr" rid="b162-tacg-5-001">162</xref>,<xref ref-type="bibr" rid="b165-tacg-5-001">165</xref> and duplications at 1q21.1<xref ref-type="bibr" rid="b159-tacg-5-001">159</xref>,<xref ref-type="bibr" rid="b164-tacg-5-001">164</xref>,<xref ref-type="bibr" rid="b166-tacg-5-001">166</xref> and 16p13.11.<xref ref-type="bibr" rid="b160-tacg-5-001">160</xref>,<xref ref-type="bibr" rid="b167-tacg-5-001">167</xref> These appear to be similarly or more variable in their expression and less penetrant with respect to schizophrenia, or indeed any major phenotype, than 22q11.2 deletions and the five emerging genetic subtypes.<xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>,<xref ref-type="bibr" rid="b168-tacg-5-001">168</xref>–<xref ref-type="bibr" rid="b179-tacg-5-001">179</xref> All await more detailed study, especially of expression in adults.</p><p><xref ref-type="table" rid="t4-tacg-5-001">Table 4</xref> outlines some of the many remaining issues with respect to clinical translation for possible genetic subtypes of schizophrenia. For instance, there are limited or inconsistent data on CNV inheritance status or comorbidity in most of the existing studies, and numerous systematic methodological issues that complicate the assessment of prevalence and penetrance.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b180-tacg-5-001">180</xref> Truly inclusive population-based prevalence samples of schizophrenia (eg, community catchments) are difficult to obtain, and many of the initial large case-control studies may have implicitly or explicitly excluded subjects with dysmorphic features, birth defects, learning difficulties, and/or known syndromes.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> Such systematic ascertainment biases in sample collection for large-scale case-control studies suggest that the prevalence of genomic disorders in schizophrenia may be underestimated. As an example, the expected prevalence of 22q11.2 deletions in schizophrenia is about 1%,<xref ref-type="bibr" rid="b65-tacg-5-001">65</xref>,<xref ref-type="bibr" rid="b181-tacg-5-001">181</xref> but a pooled estimated prevalence based on large consortium-based case-control studies is approximately 0.3%.<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> There are also few data concerning fundamental issues such as the possible effects of sex, ethnicity (most studies to date have involved Caucasians), or sampling from genetic isolates. Nonetheless, this initial wave of genome-wide studies of CNV provides replicated associations of schizophrenia with specific rare variants. This supports a more general mutational mechanism involving large rare CNV that substantially elevate risk for schizophrenia, especially more developmental forms of the disease.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b182-tacg-5-001">182</xref></p></sec><sec sec-type="discussion"><title>Neurodevelopmental implications</title><p>Notably, many of the structural variants associated with schizophrenia implicate a dosage effect of neurodevelopmental genes involved with neuronal proliferation, migration, or synapse formation.<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref>,<xref ref-type="bibr" rid="b182-tacg-5-001">182</xref> Although there are few studies that have examined age at onset of schizophrenia,<xref ref-type="bibr" rid="b166-tacg-5-001">166</xref> it may be that rare CNV have a greater impact on such genes in individuals with younger onset (eg, childhood, age <12 years) compared with onset at older ages.<xref ref-type="bibr" rid="b182-tacg-5-001">182</xref> This would be consistent with a previously reported greater prevalence of chromosomal abnormalities and 22q11.2 deletions in childhood-onset schizophrenia.<xref ref-type="bibr" rid="b183-tacg-5-001">183</xref> Several other lines of evidence, including brain imaging, premorbid clinical signs, and associations with minor dysmorphic features, have previously indicated that early changes in neurodevelopment may be involved in the pathogenesis of schizophrenia.<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref>,<xref ref-type="bibr" rid="b35-tacg-5-001">35</xref>,<xref ref-type="bibr" rid="b184-tacg-5-001">184</xref> The current genetic neurodevelopmental model of the etiopathogenesis of schizophrenia (<xref ref-type="fig" rid="f1-tacg-5-001">Figure 1</xref>) has important consequences with respect to the potential for pre-symptomatic prediction and, ultimately, attenuation, delay, or prevention of psychosis, as well as present-day genetic counseling (outlined below).</p></sec><sec><title>Clinical relevance</title><p>Use of 22q11.2DS as the benchmark for clinical applicability of molecular genetics in schizophrenia highlights the gaps that currently exist at the level of translating recent genetic results involving other large rare CNV to inform clinical management of patients (<xref ref-type="table" rid="t4-tacg-5-001">Table 4</xref>). Optimism about eventual direct benefits for patients and their families stems from the observations that effect sizes are generally large and that the spectrum of disorders involved in variable expression may tend to be multisystem and/or developmental in nature. This may be related to the multiple genes usually involved in large CNV, and in turn suggests that penetrance for any observable phenotype, as opposed to schizophrenia per se, will be fairly high. Meaningful prediction of some associated conditions would then be possible, creating opportunities for anticipatory care and improved medical management, as already exist for 22q11.2DS.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> Eventually, such genetic variants may also assist in diagnostic subtyping of schizophrenia.</p><p>Psychiatric disorders in general appear to have a poorly understood, nuanced connection to the various associated structural variants.<xref ref-type="bibr" rid="b153-tacg-5-001">153</xref> Determinants of disease specificity may be other, perhaps more common, genetic, epigenetic, stochastic, and/or environmental modifiers. There has been little research as yet on such additional factors (<xref ref-type="table" rid="t4-tacg-5-001">Table 4</xref>).<xref ref-type="bibr" rid="b185-tacg-5-001">185</xref> Likely the research that will have the most clinical impact will involve unbiased sampling, family studies, and detailed study of the variable expression and natural history of individual variants. This will in turn facilitate specific care recommendations and prediction of comorbidities, and eventually prognosis and drug response (<xref ref-type="table" rid="t4-tacg-5-001">Table 4</xref>).<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> To date, in order to gain sample sizes sufficient to detect signals in genetically heterogeneous populations, many researchers have sacrificed: (1) detailed phenotyping of the probands, (2) the ability to return to individual participants after analyses, and (3) the familial context necessary to assess de novo status and segregation patterns. These features represent, from a clinician’s point of view, unfortunate consequences of the study design of much of the large-scale genetics research conducted thus far in the twenty-first century. The longstanding practice of DNA sample anonymity, and other formal barriers between research participation and clinical care, is more and more at odds with a conflicting “duty to warn” in this new era of molecular medicine, where actionable and clinically relevant information is increasingly likely to be obtained.<xref ref-type="bibr" rid="b186-tacg-5-001">186</xref>,<xref ref-type="bibr" rid="b187-tacg-5-001">187</xref> Researchers, clinicians, and genetic counselors must begin to consider new strategies for when and how to routinely return to genotypic information and subsequently inform research participants and their clinicians of medically pertinent findings, keeping in mind that the interpretation of any particular variant is subject to change as new data accrues.</p><p>Lack of data on potential utility at this time, especially given limited resources, suggests that clinical genome-wide microarray testing is not yet justified for individuals with schizophrenia, except for the minority with syndromic and/or neurodevelopmental features such as mental retardation or multiple congenital anomalies.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref>,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref>,<xref ref-type="bibr" rid="b65-tacg-5-001">65</xref> Similarly, calls for routine targeted clinical testing on the basis of a single study where penetrance and information about expression remain unknown (eg, 7q36.3 duplications of various sizes implicating the <italic>VIPR2</italic> gene<xref ref-type="bibr" rid="b188-tacg-5-001">188</xref>) appear dangerously premature. The effectiveness of personal genomic information in tailoring interventions and improving health outcomes has not yet been convincingly demonstrated for emerging genetic subtypes of schizophrenia, nor for susceptibility factors that may be relevant for this complex disease. There are also limited to no data with respect to the ethical, legal, social, and economic implications of widespread personal genomic testing.<xref ref-type="bibr" rid="b189-tacg-5-001">189</xref> As for other diseases like ASDs,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref>,<xref ref-type="bibr" rid="b190-tacg-5-001">190</xref> careful consideration and professional consensus are needed to decide how to apply such genomic knowledge in clinical practice. Use of well-recognized standards and guidelines for clinical genetic testing, such as the ACCE Model Process for Evaluating Genetic Tests (available from: <ext-link ext-link-type="uri" xlink:href="www.cdc.gov/genomics/gtesting/ACCE/">www.cdc.gov/genomics/gtesting/ACCE/</ext-link>), may be helpful in this regard. Their application quickly exposes the many gaps in our fundamental knowledge base with respect to the clinical and analytic validity, and clinical utility, of genetic testing for most CNV in schizophrenia, particularly compared with other diseases and genetic variants such as breast/ovarian cancer and <italic>BRCA1</italic> and <italic>BRCA2</italic> mutations.<xref ref-type="bibr" rid="b191-tacg-5-001">191</xref></p></sec></sec></sec><sec><title>Genetic risk and counseling issues</title><p>Genetic counseling for schizophrenia largely continues to focus on recurrence risk based on family history, but recent molecular genetic discoveries are now having a significant impact in specific cases. Post-onset (ie, phenotype first), the identification and disclosure of a well-established genetic variant (eg, a 22q11.2 deletion) that is strongly associated with a stigmatized illness like schizophrenia may be highly valued by the patient and family for its explanatory value.<xref ref-type="bibr" rid="b186-tacg-5-001">186</xref>,<xref ref-type="bibr" rid="b192-tacg-5-001">192</xref> Such variants also provide the potential to inform reproductive decision making, including the possible availability of prenatal detection.<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> Even in the absence of such genetic variants, genetic counseling for schizophrenia may still represent an informative and therapeutic intervention. However, there are limited empiric data about potential benefits at present.</p><sec><title>Genomic disorders and genetic subtypes</title><p>Identifying genetic subtypes of schizophrenia offers new possibilities with respect to recurrence risk prediction. In the case of an individual with 22q11.2DS-schizophrenia and no other affected relatives (including the spouse or partner), for example, knowledge of the proband’s 22q11.2 deletion bifurcates the risk scenario. Transmission of the 22q11.2 deletion would imply a recurrence risk for schizophrenia of approximately 20%–25% in each offspring, whereas a failure to transmit the deletion would theoretically decrease that risk to the standard population rate (~1%). With no knowledge about the 22q11.2 deletion status, offspring would have an a priori averaged (though individually far less informative) recurrence risk for schizophrenia that is comparable to the standard empiric recurrence risk of 13%.<xref ref-type="bibr" rid="b20-tacg-5-001">20</xref>,<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref> Also, identification of a de novo 22q11.2 deletion, or other putatively causal de novo CNV, in an individual with schizophrenia would be expected to lower the recurrence risk for siblings and nieces/nephews to nearly the population rate.<xref ref-type="bibr" rid="b10-tacg-5-001">10</xref> We note from experience that for schizophrenia the risk of recurrence in siblings and nieces/nephews is the dominant concern expressed in most genetic counseling sessions, given the significantly decreased reproductive fitness associated with schizophrenia and concomitantly few direct offspring.<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref>,<xref ref-type="bibr" rid="b193-tacg-5-001">193</xref>,<xref ref-type="bibr" rid="b194-tacg-5-001">194</xref></p><p>As new diagnoses of specific genomic disorders and increasing evidence for their involvement in schizophrenia flood clinical practice, the need for more psychiatric genetic counseling research and training will be increasingly apparent. First, the association of specific large rare CNV with schizophrenia, as outlined above (<xref ref-type="table" rid="t3-tacg-5-001">Tables 3</xref> and <xref ref-type="table" rid="t4-tacg-5-001">4</xref>), effectively means that incidental predictive “genetic testing” for schizophrenia is now a reality of clinical practice, because of the use of clinical microarrays as a first-tier diagnostic test for developmental delay/mental retardation, multiple congenital anomalies (even in utero), or ASD.<xref ref-type="bibr" rid="b10-tacg-5-001">10</xref>,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref> Proposed benefits and disadvantages of predictive testing are discussed elsewhere.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b195-tacg-5-001">195</xref>,<xref ref-type="bibr" rid="b196-tacg-5-001">196</xref> Genetic counselors, however, may be reluctant to disclose the possibility of psychotic illness to parents even in the context of well-established risk factors such as 22q11.2 deletions. Stigma,<xref ref-type="bibr" rid="b197-tacg-5-001">197</xref> lack of knowledge about the illness and its treatment, and concerns about generating anxiety<xref ref-type="bibr" rid="b79-tacg-5-001">79</xref> may play a role in deferral or non-disclosure,<xref ref-type="bibr" rid="b198-tacg-5-001">198</xref> despite some evidence that opportunities to anticipate and prepare for such an illness would have been valued by the parents. <xref ref-type="bibr" rid="b186-tacg-5-001">186</xref> Second, genetic counseling of the adolescent and adult patients themselves may be complicated by cognitive impairments and/or psychiatric symptoms.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b199-tacg-5-001">199</xref> There are surprisingly few empirical studies of the optimal content and process, and of the effectiveness and ensuing outcomes, of genetic counseling in these instances,<xref ref-type="bibr" rid="b199-tacg-5-001">199</xref>,<xref ref-type="bibr" rid="b200-tacg-5-001">200</xref> even for well-recognized genomic disorders like 22q11.2DS<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref> or Williams syndrome.<xref ref-type="bibr" rid="b201-tacg-5-001">201</xref></p><p>On the other hand, clinical microarrays also give results unrelated to current genomic disorders and about which there is much uncertainty with respect to interpretation. Today, proposed workflow algorithms for determining pathogenicity are likely to label most individual CNV identified, other than the relatively established like those underlying 22q11.2DS and other genomic disorders, as “variants of unknown significance” or “VOUS.”<xref ref-type="bibr" rid="b153-tacg-5-001">153</xref>,<xref ref-type="bibr" rid="b202-tacg-5-001">202</xref> This is of particular concern for smaller (atypical) rare CNV at loci that may be associated with emerging genetic subtypes of, or possible susceptibility factors for, schizophrenia. The nature of schizophrenia poses additional challenges. For example, parents of adult patients are less likely to be available for testing to determine de novo/inherited status, and patients may be poor historians with respect to medical and/or family history. Clinical interpretation of many CNV findings will thus remain a major challenge for the foreseeable future.</p></sec><sec><title>Familial schizophrenia</title><p>Individuals from multiplex families arguably have the greatest need for risk prediction and genetic counseling. However, empiric recurrence risk figures cannot be quantitatively modified to account for multiple affected relatives or a bilineal (ie, maternal and paternal) family history.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b203-tacg-5-001">203</xref> The sole exceptions relate to the situations where both parents, or one parent and one sibling, are affected, for which some recurrence risk data are available.<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b204-tacg-5-001">204</xref> There is also no ability to adjust risk to take into account relatives with schizophrenia spectrum conditions and/or other neuropsychiatric diseases.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b203-tacg-5-001">203</xref> Also, unlike in Huntington disease before mutation identification, <xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b205-tacg-5-001">205</xref>,<xref ref-type="bibr" rid="b206-tacg-5-001">206</xref> knowledge of linkage or association information where it exists for individual families cannot be meaningfully incorporated into illness prognostication, given the modest effect size of alleles identified.</p><p>As for any individual with schizophrenia, clinicians should be aware of features consistent with testable conditions like 22q11.2DS. However, 22q11.2 deletions are less likely to be co-segregating with schizophrenia in multiply affected families, as they are associated with a strong negative selective pressure.<xref ref-type="bibr" rid="b57-tacg-5-001">57</xref> Other large rare CNV associated with schizophrenia, for example, microduplications not associated with multisystem/syndromic features,<xref ref-type="bibr" rid="b157-tacg-5-001">157</xref>,<xref ref-type="bibr" rid="b180-tacg-5-001">180</xref> may have less effect on reproductive fitness and thus a higher likelihood of contributing to the burden of illness in multiply affected families, though this remains to be shown. There is growing empirical<xref ref-type="bibr" rid="b207-tacg-5-001">207</xref> and theoretical<xref ref-type="bibr" rid="b208-tacg-5-001">208</xref>,<xref ref-type="bibr" rid="b209-tacg-5-001">209</xref> evidence that, as for Parkinson disease,<xref ref-type="bibr" rid="b210-tacg-5-001">210</xref> familial and “sporadic” schizophrenia may not be molecularly distinct entities. This underscores the need for a greater focus in future studies on both the inheritance status of genetic variants shown to be associated with schizophrenia, and on the extent of co-segregation of these variants with other neuropsychiatric illness and developmental conditions within families.</p></sec><sec><title>Idiopathic schizophrenia</title><p>Often overlooked in our collective enthusiasm for the promise of new genetic discoveries are the sobering realizations that the vast majority of cases of schizophrenia are “idiopathic” and that, as for most conditions,<xref ref-type="bibr" rid="b211-tacg-5-001">211</xref> family history remains the cornerstone for individualized disease prediction. When the schizophrenia is not a syndromic form of the illness,<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref> of genetically testable origin,<xref ref-type="bibr" rid="b61-tacg-5-001">61</xref> or originating in the context of a multiplex family, patients and their relatives are unlikely to be seen by a genetics professional unless presented with an unrelated concern.<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref> Much has been written and repeated over the past several decades about the optimal content and process of “multifactorial” genetic counseling,<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b147-tacg-5-001">147</xref>,<xref ref-type="bibr" rid="b196-tacg-5-001">196</xref>,<xref ref-type="bibr" rid="b204-tacg-5-001">204</xref>,<xref ref-type="bibr" rid="b212-tacg-5-001">212</xref>–<xref ref-type="bibr" rid="b214-tacg-5-001">214</xref> despite low rates of genetic counseling referrals<xref ref-type="bibr" rid="b215-tacg-5-001">215</xref> and a continued scarcity of evidence in support of the desirability<xref ref-type="bibr" rid="b216-tacg-5-001">216</xref> or effectiveness<xref ref-type="bibr" rid="b217-tacg-5-001">217</xref> of the genetic counseling intervention. To assess these key issues, and also prepare for the growing role of personalized molecular genetic information, there is an urgent need for data-driven reports of the genetic counseling of patients with idiopathic schizophrenia and their relatives.</p><p>Recent advances in schizophrenia genetics may still be germane to contemporary genetic counseling however, even in the absence of personalized application. For example, presenting schizophrenia to consultands as a neurodevelopmental disorder (<xref ref-type="fig" rid="f1-tacg-5-001">Figure 1</xref>),<xref ref-type="bibr" rid="b35-tacg-5-001">35</xref> with psychosis as a later stage manifestation often preceded by a prodromal period,<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref> has the potential to further modify false beliefs that upbringing, lifestyle decisions, or other “triggers”<xref ref-type="bibr" rid="b204-tacg-5-001">204</xref> are either necessary or sufficient to cause an illness that otherwise would not have developed. Proof that de novo mutations play an important causal role in some cases may help in dispelling a popular misconception<xref ref-type="bibr" rid="b218-tacg-5-001">218</xref> that “genetic” and “inherited” are synonymous terms. Especially in the absence of an affected first- or second-degree ancestor, de novo mutation is a highly plausible theory of causation that may decrease a sense of family blame or shame. Finally, presenting evidence for genetic and epigenetic differences between monozygotic twins can help to explain discordant twin pairs without needing to resort to the unsupported assumption of powerful environmental factors in these rare cases.<xref ref-type="bibr" rid="b219-tacg-5-001">219</xref>–<xref ref-type="bibr" rid="b222-tacg-5-001">222</xref> The role of independent environmental factors<xref ref-type="bibr" rid="b29-tacg-5-001">29</xref> may be less, and that of gene-environment interactions<xref ref-type="bibr" rid="b25-tacg-5-001">25</xref>,<xref ref-type="bibr" rid="b223-tacg-5-001">223</xref>,<xref ref-type="bibr" rid="b224-tacg-5-001">224</xref> and stochastic effects<xref ref-type="bibr" rid="b225-tacg-5-001">225</xref>,<xref ref-type="bibr" rid="b226-tacg-5-001">226</xref> may be greater, than initially supposed.</p><p>As yet, the full “risk architecture” of schizophrenia, and the extent to which risk factors may be modifiable, is unknown.<xref ref-type="bibr" rid="b2-tacg-5-001">2</xref> With respect to idiopathic schizophrenia, there is a forced reliance on family history and associated crude empiric recurrence risks, unmodified quantitatively by any other clinical or demographic variables.<xref ref-type="bibr" rid="b203-tacg-5-001">203</xref> Few attempts have been made to update or validate these recurrence risks, despite the potential increase in the proportion of individuals with schizophrenia who partner with someone else with schizophrenia (ie, assortative mating),<xref ref-type="bibr" rid="b227-tacg-5-001">227</xref> new conceptualizations of the genetically relevant schizophrenia spectrum,<xref ref-type="bibr" rid="b3-tacg-5-001">3</xref> and increasing opportunities for molecular characterization. Initial attempts to generate a “risk score” from multiple variants with weak association with schizophrenia may be promising avenues for future research,<xref ref-type="bibr" rid="b131-tacg-5-001">131</xref>,<xref ref-type="bibr" rid="b228-tacg-5-001">228</xref>,<xref ref-type="bibr" rid="b229-tacg-5-001">229</xref> but are not yet meaningful in a clinical genetic counseling context. In addition, the factors of primary interest in genetic counseling (ie, those that increase individual recurrence risk substantially) do not necessarily have much effect on average risk, the primary focus of most retrospective studies of schizophrenia, and vice versa.<xref ref-type="bibr" rid="b230-tacg-5-001">230</xref> Partial risk prediction as afforded by proven moderate to high penetrance variants such as 22q11.2 deletions may be the best case scenario. There are likely to be fundamental limits on precise individualized genetic risk prediction due to the complex architecture of common traits, including common variants of very small effect, rare variants that cannot be fully enumerated, and complex epistatic interactions, as well as stochastic and possible environmental factors.<xref ref-type="bibr" rid="b231-tacg-5-001">231</xref> The potential “added value” of genome-wide data (eg, derived from next-generation sequencing) in tailoring risk estimates would also need to be weighed against many other factors. These include the cost of, and expertise needed for, the molecular analysis (which is still prohibitive for widespread use, particularly in publicly funded health care systems) and the interpretation of results (as great or greater than molecular analytic costs, and less likely to decrease over time).<xref ref-type="bibr" rid="b231-tacg-5-001">231</xref> Such barriers will impede widespread application of new genetic technologies in clinical practice more generally for the foreseeable future. Personal genome sequencing as a single universal genetic test that is cost-effective and of broadly applicable clinical utility remains a distant, though much wished for, prospect.<xref ref-type="bibr" rid="b232-tacg-5-001">232</xref></p></sec></sec><sec><title>Conclusion</title><p>Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and little is known about the associated pathophysiology apart from strong evidence for neurodevelopmental origins. The elucidation of specific causes and mechanisms for schizophrenia that is beginning to be derived from advances in molecular genetics and related research promises to help many families afflicted with this illness. However, much work needs to be done to move the recent surge of genetic research discoveries into the clinic. In particular, specific large rare structural variants (CNV) have been convincingly implicated in targeted studies over two decades (with respect to 22q11.2 deletions) and more recently in several large-scale genome-wide case-control studies of schizophrenia. Clinical interpretation of most individual loci remains unclear as yet because the associated epidemiology and basic genetic parameters (such as penetrance and expression) are not yet well characterized. For now, 22q11.2 deletions represent the cutting-edge of clinically applicable molecular genetics in schizophrenia. New opportunities in risk prediction and genetic counseling are exciting avenues for future research.</p></sec></body><back><ack><title>Acknowledgments</title><p>The authors thank Sean Bekeschus for his assistance with aesthetic design of the figure. This work was supported by Canadian Institutes of Health Research grants (MOP-97800, MOP-111238, MOP-53216), a Vanier Canada Graduate Scholarship (GC), and a Canada Research Chair in Schizophrenia Genetics and Genomic Disorders (ASB).</p></ack><fn-group><fn id="fn1-tacg-5-001"><p><bold>Disclosure</bold></p><p>The authors have no actual or potential conflicts of interest to disclose in this work.</p></fn></fn-group><ref-list><title>References</title><ref id="b1-tacg-5-001"><label>1</label><element-citation publication-type="journal"><article-title>Where next with psychiatric illness?</article-title><source>Nature</source><year>1988</year><volume>336</volume><issue>6195</issue><fpage>95</fpage><lpage>96</lpage><pub-id pub-id-type="pmid">3185737</pub-id></element-citation></ref><ref id="b2-tacg-5-001"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Insel</surname><given-names>TR</given-names></name></person-group><article-title>Rethinking schizophrenia</article-title><source>Nature</source><year>2010</year><volume>468</volume><issue>7321</issue><fpage>187</fpage><lpage>193</lpage><pub-id pub-id-type="pmid">21068826</pub-id></element-citation></ref><ref id="b3-tacg-5-001"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Scherer</surname><given-names>SW</given-names></name><name><surname>Brzustowicz</surname><given-names>LM</given-names></name></person-group><article-title>Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease</article-title><source>Am J Psychiatry</source><year>2010</year><volume>167</volume><issue>8</issue><fpage>899</fpage><lpage>914</lpage><pub-id pub-id-type="pmid">20439386</pub-id></element-citation></ref><ref id="b4-tacg-5-001"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gejman</surname><given-names>PV</given-names></name><name><surname>Sanders</surname><given-names>AR</given-names></name><name><surname>Kendler</surname><given-names>KS</given-names></name></person-group><article-title>Genetics of schizophrenia: new findings and challenges</article-title><source>Annu Rev Genomics Hum Genet</source><year>2011</year><volume>12</volume><fpage>121</fpage><lpage>144</lpage><pub-id pub-id-type="pmid">21639796</pub-id></element-citation></ref><ref id="b5-tacg-5-001"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hochstenbach</surname><given-names>R</given-names></name><name><surname>Buizer-Voskamp</surname><given-names>JE</given-names></name><name><surname>Vorstman</surname><given-names>JA</given-names></name><name><surname>Ophoff</surname><given-names>RA</given-names></name></person-group><article-title>Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research</article-title><source>Cytogenet Genome Res</source><year>2011</year><volume>135</volume><issue>3–4</issue><fpage>174</fpage><lpage>202</lpage><pub-id pub-id-type="pmid">22056632</pub-id></element-citation></ref><ref id="b6-tacg-5-001"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y</given-names></name><name><surname>Zerwas</surname><given-names>S</given-names></name><name><surname>Trace</surname><given-names>SE</given-names></name><name><surname>Sullivan</surname><given-names>PF</given-names></name></person-group><article-title>Schizophrenia genetics: where next?</article-title><source>Schizophr Bull</source><year>2011</year><volume>37</volume><issue>3</issue><fpage>456</fpage><lpage>463</lpage><pub-id pub-id-type="pmid">21505112</pub-id></element-citation></ref><ref id="b7-tacg-5-001"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kirov</surname><given-names>G</given-names></name></person-group><article-title>The role of copy number variation in schizophrenia</article-title><source>Expert Rev Neurother</source><year>2010</year><volume>10</volume><issue>1</issue><fpage>25</fpage><lpage>32</lpage><pub-id pub-id-type="pmid">20021318</pub-id></element-citation></ref><ref id="b8-tacg-5-001"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rodriguez-Murillo</surname><given-names>L</given-names></name><name><surname>Gogos</surname><given-names>JA</given-names></name><name><surname>Karayiorgou</surname><given-names>M</given-names></name></person-group><article-title>The genetic architecture of schizophrenia: new mutations and emerging paradigms</article-title><source>Annu Rev Med</source><year>2012</year><volume>63</volume><fpage>63</fpage><lpage>80</lpage><pub-id pub-id-type="pmid">22034867</pub-id></element-citation></ref><ref id="b9-tacg-5-001"><label>9</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EWC</given-names></name><name><surname>Hodgkinson</surname><given-names>KA</given-names></name></person-group><article-title>Genetics of schizophrenia and psychotic disorders</article-title><person-group person-group-type="editor"><name><surname>Smoller</surname><given-names>JW</given-names></name><name><surname>Rosen Sheidley</surname><given-names>B</given-names></name><name><surname>Tsuang</surname><given-names>MT</given-names></name></person-group><source>Psychiatric Genetics: Applications in Clinical Practice</source><publisher-loc>Arlington</publisher-loc><publisher-name>American Psychiatric Publishing, Inc</publisher-name><year>2008</year><fpage>99</fpage><lpage>130</lpage></element-citation></ref><ref id="b10-tacg-5-001"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Collier</surname><given-names>DA</given-names></name><name><surname>Vassos</surname><given-names>E</given-names></name><name><surname>Holden</surname><given-names>S</given-names></name><name><surname>Patch</surname><given-names>C</given-names></name><name><surname>McGuire</surname><given-names>P</given-names></name><name><surname>Lewis</surname><given-names>C</given-names></name></person-group><article-title>Advances in the genetics of schizophrenia: will high-risk copy number variants be useful in clinical genetics or diagnostics?</article-title><source>F1000 Med Rep</source><year>2009</year><volume>1</volume><fpage>61</fpage><pub-id pub-id-type="pmid">20948719</pub-id></element-citation></ref><ref id="b11-tacg-5-001"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moreno-De-Luca</surname><given-names>D</given-names></name><name><surname>Cubells</surname><given-names>JF</given-names></name></person-group><article-title>Copy number variants: a new molecular frontier in clinical psychiatry</article-title><source>Curr Psychiatry Rep</source><year>2011</year><volume>13</volume><issue>2</issue><fpage>129</fpage><lpage>137</lpage><pub-id pub-id-type="pmid">21253883</pub-id></element-citation></ref><ref id="b12-tacg-5-001"><label>12</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Mueser</surname><given-names>KT</given-names></name><name><surname>Jeste</surname><given-names>DV</given-names></name></person-group><source>Clinical Handbook of Schizophrenia</source><publisher-loc>New York</publisher-loc><publisher-name>Guilford Press</publisher-name><year>2008</year></element-citation></ref><ref id="b13-tacg-5-001"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brzustowicz</surname><given-names>LM</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Phenotype matters: the case for careful characterization of relevant traits</article-title><source>Am J Psychiatry</source><year>2008</year><volume>165</volume><issue>9</issue><fpage>1096</fpage><lpage>1098</lpage><pub-id pub-id-type="pmid">18765489</pub-id></element-citation></ref><ref id="b14-tacg-5-001"><label>14</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Harper</surname><given-names>PS</given-names></name></person-group><source>A Short History of Medical Genetics</source><publisher-loc>New York</publisher-loc><publisher-name>Oxford University Press</publisher-name><year>2008</year></element-citation></ref><ref id="b15-tacg-5-001"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cannon</surname><given-names>TD</given-names></name><name><surname>Kaprio</surname><given-names>J</given-names></name><name><surname>Lonnqvist</surname><given-names>J</given-names></name><name><surname>Huttunen</surname><given-names>M</given-names></name><name><surname>Koskenvuo</surname><given-names>M</given-names></name></person-group><article-title>The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study</article-title><source>Arch Gen Psychiatry</source><year>1998</year><volume>55</volume><issue>1</issue><fpage>67</fpage><lpage>74</lpage><pub-id pub-id-type="pmid">9435762</pub-id></element-citation></ref><ref id="b16-tacg-5-001"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cardno</surname><given-names>AG</given-names></name><name><surname>Gottesman</surname><given-names>II</given-names></name></person-group><article-title>Twin studies of schizophrenia: from bow-and- arrow concordances to star wars Mx and functional genomics</article-title><source>Am J Med Genet</source><year>2000</year><volume>97</volume><issue>1</issue><fpage>12</fpage><lpage>17</lpage><pub-id pub-id-type="pmid">10813800</pub-id></element-citation></ref><ref id="b17-tacg-5-001"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kendler</surname><given-names>KS</given-names></name><name><surname>Diehl</surname><given-names>SR</given-names></name></person-group><article-title>The genetics of schizophrenia: a current, genetic-epidemiologic perspective</article-title><source>Schizophr Bull</source><year>1993</year><volume>19</volume><issue>2</issue><fpage>261</fpage><lpage>285</lpage><pub-id pub-id-type="pmid">8322035</pub-id></element-citation></ref><ref id="b18-tacg-5-001"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kirov</surname><given-names>G</given-names></name><name><surname>O’Donovan</surname><given-names>MC</given-names></name><name><surname>Owen</surname><given-names>MJ</given-names></name></person-group><article-title>Finding schizophrenia genes</article-title><source>J Clin Invest</source><year>2005</year><volume>115</volume><issue>6</issue><fpage>1440</fpage><lpage>1448</lpage><pub-id pub-id-type="pmid">15931379</pub-id></element-citation></ref><ref id="b19-tacg-5-001"><label>19</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Gottesman</surname><given-names>II</given-names></name><name><surname>Shields</surname><given-names>J</given-names></name><name><surname>Hanson</surname><given-names>DR</given-names></name></person-group><source>Schizophrenia, the Epigenetic Puzzle</source><publisher-loc>New York</publisher-loc><publisher-name>Cambridge University Press</publisher-name><year>1982</year></element-citation></ref><ref id="b20-tacg-5-001"><label>20</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Gottesman</surname><given-names>II</given-names></name><name><surname>Wolfgram</surname><given-names>DL</given-names></name></person-group><source>Schizophrenia Genesis: The Origins of Madness</source><publisher-loc>New York</publisher-loc><publisher-name>Freeman</publisher-name><year>1991</year></element-citation></ref><ref id="b21-tacg-5-001"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kendler</surname><given-names>KS</given-names></name><name><surname>Gruenberg</surname><given-names>AM</given-names></name><name><surname>Tsuang</surname><given-names>MT</given-names></name></person-group><article-title>Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients. A family study using DSM-III criteria</article-title><source>Arch Gen Psychiatry</source><year>1985</year><volume>42</volume><issue>8</issue><fpage>770</fpage><lpage>779</lpage><pub-id pub-id-type="pmid">4015321</pub-id></element-citation></ref><ref id="b22-tacg-5-001"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lowing</surname><given-names>PA</given-names></name><name><surname>Mirsky</surname><given-names>AF</given-names></name><name><surname>Pereira</surname><given-names>R</given-names></name></person-group><article-title>The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoptee study data</article-title><source>Am J Psychiatry</source><year>1983</year><volume>140</volume><issue>9</issue><fpage>1167</fpage><lpage>1171</lpage><pub-id pub-id-type="pmid">6614222</pub-id></element-citation></ref><ref id="b23-tacg-5-001"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moldin</surname><given-names>SO</given-names></name><name><surname>Gottesman</surname><given-names>II</given-names></name></person-group><article-title>At issue: genes, experience, and chance in schizophrenia – positioning for the 21st century</article-title><source>Schizophr Bull</source><year>1997</year><volume>23</volume><issue>4</issue><fpage>547</fpage><lpage>561</lpage><pub-id pub-id-type="pmid">9365994</pub-id></element-citation></ref><ref id="b24-tacg-5-001"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tienari</surname><given-names>PJ</given-names></name><name><surname>Wynne</surname><given-names>LC</given-names></name></person-group><article-title>Adoption studies of schizophrenia</article-title><source>Ann Med</source><year>1994</year><volume>26</volume><issue>4</issue><fpage>233</fpage><lpage>237</lpage><pub-id pub-id-type="pmid">7946240</pub-id></element-citation></ref><ref id="b25-tacg-5-001"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>AbdelMalik</surname><given-names>P</given-names></name><name><surname>Husted</surname><given-names>J</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Childhood head injury and expression of schizophrenia in multiply affected families</article-title><source>Arch Gen Psychiatry</source><year>2003</year><volume>60</volume><issue>3</issue><fpage>231</fpage><lpage>236</lpage><pub-id pub-id-type="pmid">12622655</pub-id></element-citation></ref><ref id="b26-tacg-5-001"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Byrne</surname><given-names>M</given-names></name><name><surname>Browne</surname><given-names>R</given-names></name><name><surname>Mulryan</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Labour and delivery complications and schizophrenia. Case-control study using contemporaneous labour ward records</article-title><source>Br J Psychiatry</source><year>2000</year><volume>176</volume><fpage>531</fpage><lpage>536</lpage><pub-id pub-id-type="pmid">10974958</pub-id></element-citation></ref><ref id="b27-tacg-5-001"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Henquet</surname><given-names>C</given-names></name><name><surname>Di Forti</surname><given-names>M</given-names></name><name><surname>Morrison</surname><given-names>P</given-names></name><name><surname>Kuepper</surname><given-names>R</given-names></name><name><surname>Murray</surname><given-names>RM</given-names></name></person-group><article-title>Gene-environment interplay between cannabis and psychosis</article-title><source>Schizophr Bull</source><year>2008</year><volume>34</volume><issue>6</issue><fpage>1111</fpage><lpage>1121</lpage><pub-id pub-id-type="pmid">18723841</pub-id></element-citation></ref><ref id="b28-tacg-5-001"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McGuffin</surname><given-names>P</given-names></name><name><surname>Asherson</surname><given-names>P</given-names></name><name><surname>Owen</surname><given-names>M</given-names></name><name><surname>Farmer</surname><given-names>A</given-names></name></person-group><article-title>The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia?</article-title><source>Br J Psychiatry</source><year>1994</year><volume>164</volume><issue>5</issue><fpage>593</fpage><lpage>599</lpage><pub-id pub-id-type="pmid">7921708</pub-id></element-citation></ref><ref id="b29-tacg-5-001"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matheson</surname><given-names>SL</given-names></name><name><surname>Shepherd</surname><given-names>AM</given-names></name><name><surname>Laurens</surname><given-names>KR</given-names></name><name><surname>Carr</surname><given-names>VJ</given-names></name></person-group><article-title>A systematic meta-review grading the evidence for non-genetic risk factors and putative antecedents of schizophrenia</article-title><source>Schizophr Res</source><year>2011</year><volume>133</volume><issue>1–3</issue><fpage>133</fpage><lpage>142</lpage><pub-id pub-id-type="pmid">21999904</pub-id></element-citation></ref><ref id="b30-tacg-5-001"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moore</surname><given-names>TH</given-names></name><name><surname>Zammit</surname><given-names>S</given-names></name><name><surname>Lingford-Hughes</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review</article-title><source>Lancet</source><year>2007</year><volume>370</volume><issue>9584</issue><fpage>319</fpage><lpage>328</lpage><pub-id pub-id-type="pmid">17662880</pub-id></element-citation></ref><ref id="b31-tacg-5-001"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tienari</surname><given-names>P</given-names></name></person-group><article-title>Implications of adoption studies on schizophrenia</article-title><source>Br J Psychiatry Suppl</source><year>1992</year><volume>18</volume><fpage>52</fpage><lpage>58</lpage><pub-id pub-id-type="pmid">1389042</pub-id></element-citation></ref><ref id="b32-tacg-5-001"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wahlberg</surname><given-names>KE</given-names></name><name><surname>Wynne</surname><given-names>LC</given-names></name><name><surname>Oja</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia</article-title><source>Am J Psychiatry</source><year>1997</year><volume>154</volume><issue>3</issue><fpage>355</fpage><lpage>362</lpage><pub-id pub-id-type="pmid">9054783</pub-id></element-citation></ref><ref id="b33-tacg-5-001"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gottesman</surname><given-names>II</given-names></name><name><surname>Bertelsen</surname><given-names>A</given-names></name></person-group><article-title>Confirming unexpressed genotypes for schizophrenia. Risks in the offspring of Fischer’s Danish identical and fraternal discordant twins</article-title><source>Arch Gen Psychiatry</source><year>1989</year><volume>46</volume><issue>10</issue><fpage>867</fpage><lpage>872</lpage><pub-id pub-id-type="pmid">2802925</pub-id></element-citation></ref><ref id="b34-tacg-5-001"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kringlen</surname><given-names>E</given-names></name><name><surname>Cramer</surname><given-names>G</given-names></name></person-group><article-title>Offspring of monozygotic twins discordant for schizophrenia</article-title><source>Arch Gen Psychiatry</source><year>1989</year><volume>46</volume><issue>10</issue><fpage>873</fpage><lpage>877</lpage><pub-id pub-id-type="pmid">2802926</pub-id></element-citation></ref><ref id="b35-tacg-5-001"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>O’Neill</surname><given-names>S</given-names></name><name><surname>Brzustowicz</surname><given-names>LM</given-names></name></person-group><article-title>Genetic insights into the neurodevelopmental hypothesis of schizophrenia</article-title><source>Schizophr Bull</source><year>2001</year><volume>27</volume><issue>3</issue><fpage>417</fpage><lpage>430</lpage><pub-id pub-id-type="pmid">11596844</pub-id></element-citation></ref><ref id="b36-tacg-5-001"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Waterworth</surname><given-names>DM</given-names></name><name><surname>Brzustowicz</surname><given-names>L</given-names></name></person-group><article-title>Genetic insights into schizophrenia</article-title><source>Can J Psychiatry</source><year>2001</year><volume>46</volume><issue>2</issue><fpage>131</fpage><lpage>137</lpage><pub-id pub-id-type="pmid">11280081</pub-id></element-citation></ref><ref id="b37-tacg-5-001"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prasad</surname><given-names>KM</given-names></name><name><surname>Talkowski</surname><given-names>ME</given-names></name><name><surname>Chowdari</surname><given-names>KV</given-names></name><name><surname>McClain</surname><given-names>L</given-names></name><name><surname>Yolken</surname><given-names>RH</given-names></name><name><surname>Nimgaonkar</surname><given-names>VL</given-names></name></person-group><article-title>Candidate genes and their interactions with other genetic/environmental risk factors in the etiology of schizophrenia</article-title><source>Brain Res Bull</source><year>2010</year><volume>83</volume><issue>3–4</issue><fpage>86</fpage><lpage>92</lpage><pub-id pub-id-type="pmid">19729054</pub-id></element-citation></ref><ref id="b38-tacg-5-001"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Risch</surname><given-names>N</given-names></name></person-group><article-title>Linkage strategies for genetically complex traits. I. Multilocus models</article-title><source>Am J Hum Genet</source><year>1990</year><volume>46</volume><issue>2</issue><fpage>222</fpage><lpage>228</lpage><pub-id pub-id-type="pmid">2301392</pub-id></element-citation></ref><ref id="b39-tacg-5-001"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Phillips</surname><given-names>PC</given-names></name></person-group><article-title>Epistasis – the essential role of gene interactions in the structure and evolution of genetic systems</article-title><source>Nat Rev Genet</source><year>2008</year><volume>9</volume><issue>11</issue><fpage>855</fpage><lpage>867</lpage><pub-id pub-id-type="pmid">18852697</pub-id></element-citation></ref><ref id="b40-tacg-5-001"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Book</surname><given-names>JA</given-names></name></person-group><article-title>Schizophrenia as a gene mutation</article-title><source>Acta Genet Stat Med</source><year>1953</year><volume>4</volume><issue>2–3</issue><fpage>133</fpage><lpage>139</lpage><pub-id pub-id-type="pmid">13137881</pub-id></element-citation></ref><ref id="b41-tacg-5-001"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Penrose</surname><given-names>LS</given-names></name></person-group><article-title>Mutation in man</article-title><source>Acta Genet Stat Med</source><year>1956</year><volume>6</volume><issue>2</issue><fpage>169</fpage><lpage>182</lpage><pub-id pub-id-type="pmid">13410479</pub-id></element-citation></ref><ref id="b42-tacg-5-001"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McClellan</surname><given-names>JM</given-names></name><name><surname>Susser</surname><given-names>E</given-names></name><name><surname>King</surname><given-names>MC</given-names></name></person-group><article-title>Schizophrenia: a common disease caused by multiple rare alleles</article-title><source>Br J Psychiatry</source><year>2007</year><volume>190</volume><fpage>194</fpage><lpage>199</lpage><pub-id pub-id-type="pmid">17329737</pub-id></element-citation></ref><ref id="b43-tacg-5-001"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name></person-group><article-title>Schizophrenia and 22q11.2 deletion syndrome</article-title><source>Curr Psychiatry Rep</source><year>2008</year><volume>10</volume><issue>2</issue><fpage>148</fpage><lpage>157</lpage><pub-id pub-id-type="pmid">18474208</pub-id></element-citation></ref><ref id="b44-tacg-5-001"><label>44</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Zackai</surname><given-names>EH</given-names></name></person-group><source>The history of the 22q11.2 deletion [webpage on the Internet]</source><publisher-loc>Philadelphia, PA</publisher-loc><publisher-name>Clinical Genetics Center – The Children’s Hospital of Philadelphia</publisher-name><year>nd</year><comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://www.cbil.upenn.edu/VCFS/history.html">http://www.cbil.upenn.edu/VCFS/history.html</ext-link></comment><date-in-citation>Accessed January 4, 2012.</date-in-citation></element-citation></ref><ref id="b45-tacg-5-001"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shprintzen</surname><given-names>RJ</given-names></name><name><surname>Goldberg</surname><given-names>R</given-names></name><name><surname>Golding-Kushner</surname><given-names>KJ</given-names></name><name><surname>Marion</surname><given-names>RW</given-names></name></person-group><article-title>Late- onset psychosis in the velo-cardio-facial syndrome</article-title><source>Am J Med Genet</source><year>1992</year><volume>42</volume><issue>1</issue><fpage>141</fpage><lpage>142</lpage><pub-id pub-id-type="pmid">1308357</pub-id></element-citation></ref><ref id="b46-tacg-5-001"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Devriendt</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Practical guidelines for managing patients with 22q11.2 deletion syndrome</article-title><source>J Pediatr</source><year>2011</year><volume>159</volume><issue>2</issue><fpage>332</fpage><lpage>339</lpage><fpage>e1</fpage><pub-id pub-id-type="pmid">21570089</pub-id></element-citation></ref><ref id="b47-tacg-5-001"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Karayiorgou</surname><given-names>M</given-names></name><name><surname>Simon</surname><given-names>TJ</given-names></name><name><surname>Gogos</surname><given-names>JA</given-names></name></person-group><article-title>22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia</article-title><source>Nat Rev Neurosci</source><year>2010</year><volume>11</volume><issue>6</issue><fpage>402</fpage><lpage>416</lpage><pub-id pub-id-type="pmid">20485365</pub-id></element-citation></ref><ref id="b48-tacg-5-001"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Philip</surname><given-names>N</given-names></name><name><surname>Bassett</surname><given-names>A</given-names></name></person-group><article-title>Cognitive, behavioural and psychiatric phenotype in 22q11.2 deletion syndrome</article-title><source>Behav Genet</source><year>2011</year><volume>41</volume><issue>3</issue><fpage>403</fpage><lpage>412</lpage><pub-id pub-id-type="pmid">21573985</pub-id></element-citation></ref><ref id="b49-tacg-5-001"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sandrin-Garcia</surname><given-names>P</given-names></name><name><surname>Abramides</surname><given-names>DV</given-names></name><name><surname>Martelli</surname><given-names>LR</given-names></name><name><surname>Ramos</surname><given-names>ES</given-names></name><name><surname>Richieri- Costa</surname><given-names>A</given-names></name><name><surname>Passos</surname><given-names>GA</given-names></name></person-group><article-title>Typical phenotypic spectrum of velocardiofacial syndrome occurs independently of deletion size in chromosome 22q11.2</article-title><source>Mol Cell Biochem</source><year>2007</year><volume>303</volume><issue>1–2</issue><fpage>9</fpage><lpage>17</lpage><pub-id pub-id-type="pmid">17426930</pub-id></element-citation></ref><ref id="b50-tacg-5-001"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weksberg</surname><given-names>R</given-names></name><name><surname>Stachon</surname><given-names>AC</given-names></name><name><surname>Squire</surname><given-names>JA</given-names></name><etal></etal></person-group><article-title>Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome</article-title><source>Hum Genet</source><year>2007</year><volume>120</volume><issue>6</issue><fpage>837</fpage><lpage>845</lpage><pub-id pub-id-type="pmid">17028864</pub-id></element-citation></ref><ref id="b51-tacg-5-001"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Edelmann</surname><given-names>L</given-names></name><name><surname>Pandita</surname><given-names>RK</given-names></name><name><surname>Morrow</surname><given-names>BE</given-names></name></person-group><article-title>Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome</article-title><source>Am J Hum Genet</source><year>1999</year><volume>64</volume><issue>4</issue><fpage>1076</fpage><lpage>1086</lpage><pub-id pub-id-type="pmid">10090893</pub-id></element-citation></ref><ref id="b52-tacg-5-001"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stankiewicz</surname><given-names>P</given-names></name><name><surname>Lupski</surname><given-names>JR</given-names></name></person-group><article-title>Genome architecture, rearrangements and genomic disorders</article-title><source>Trends Genet</source><year>2002</year><volume>18</volume><issue>2</issue><fpage>74</fpage><lpage>82</lpage><pub-id pub-id-type="pmid">11818139</pub-id></element-citation></ref><ref id="b53-tacg-5-001"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Marshall</surname><given-names>CR</given-names></name><name><surname>Lionel</surname><given-names>AC</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Scherer</surname><given-names>SW</given-names></name></person-group><article-title>Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome</article-title><source>Hum Mol Genet</source><year>2008</year><volume>17</volume><issue>24</issue><fpage>4045</fpage><lpage>4053</lpage><pub-id pub-id-type="pmid">18806272</pub-id></element-citation></ref><ref id="b54-tacg-5-001"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cohen</surname><given-names>E</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Weksberg</surname><given-names>R</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Phenotype of adults with the 22q11 deletion syndrome: A review</article-title><source>Am J Med Genet</source><year>1999</year><volume>86</volume><issue>4</issue><fpage>359</fpage><lpage>365</lpage><pub-id pub-id-type="pmid">10494092</pub-id></element-citation></ref><ref id="b55-tacg-5-001"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Digilio</surname><given-names>MC</given-names></name><name><surname>Angioni</surname><given-names>A</given-names></name><name><surname>De Santis</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies</article-title><source>Clin Genet</source><year>2003</year><volume>63</volume><issue>4</issue><fpage>308</fpage><lpage>313</lpage><pub-id pub-id-type="pmid">12702165</pub-id></element-citation></ref><ref id="b56-tacg-5-001"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Tonnesen</surname><given-names>MK</given-names></name><name><surname>Laufer-Cahana</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!</article-title><source>Genet Med</source><year>2001</year><volume>3</volume><issue>1</issue><fpage>23</fpage><lpage>29</lpage><pub-id pub-id-type="pmid">11339373</pub-id></element-citation></ref><ref id="b57-tacg-5-001"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Costain</surname><given-names>G</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Silversides</surname><given-names>CK</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions</article-title><source>J Med Genet</source><year>2011</year><volume>48</volume><issue>12</issue><fpage>819</fpage><lpage>824</lpage><pub-id pub-id-type="pmid">22051516</pub-id></element-citation></ref><ref id="b58-tacg-5-001"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lupski</surname><given-names>JR</given-names></name></person-group><article-title>Genomic disorders ten years on</article-title><source>Genome Med</source><year>2009</year><volume>1</volume><issue>4</issue><fpage>42</fpage><pub-id pub-id-type="pmid">19439022</pub-id></element-citation></ref><ref id="b59-tacg-5-001"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kobrynski</surname><given-names>LJ</given-names></name><name><surname>Sullivan</surname><given-names>KE</given-names></name></person-group><article-title>Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes</article-title><source>Lancet</source><year>2007</year><volume>370</volume><issue>9596</issue><fpage>1443</fpage><lpage>1452</lpage><pub-id pub-id-type="pmid">17950858</pub-id></element-citation></ref><ref id="b60-tacg-5-001"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Sullivan</surname><given-names>KE</given-names></name></person-group><article-title>Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)</article-title><source>Medicine (Baltimore)</source><year>2011</year><volume>90</volume><issue>1</issue><fpage>1</fpage><lpage>18</lpage><pub-id pub-id-type="pmid">21200182</pub-id></element-citation></ref><ref id="b61-tacg-5-001"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>DT</given-names></name><name><surname>Adam</surname><given-names>MP</given-names></name><name><surname>Aradhya</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies</article-title><source>Am J Hum Genet</source><year>2010</year><volume>86</volume><issue>5</issue><fpage>749</fpage><lpage>764</lpage><pub-id pub-id-type="pmid">20466091</pub-id></element-citation></ref><ref id="b62-tacg-5-001"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tokuyasu</surname><given-names>TA</given-names></name><name><surname>Cotter</surname><given-names>PD</given-names></name><name><surname>Segraves</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Detection of single clone deletions using array CGH: identification of submicroscopic deletions in the 22q11.2 deletion syndrome as a model system</article-title><source>Am J Med Genet A</source><year>2007</year><volume>143A</volume><issue>9</issue><fpage>925</fpage><lpage>932</lpage><pub-id pub-id-type="pmid">17394204</pub-id></element-citation></ref><ref id="b63-tacg-5-001"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Husted</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Clinical features of 78 adults with 22q11 Deletion Syndrome</article-title><source>Am J Med Genet A</source><year>2005</year><volume>138</volume><issue>4</issue><fpage>307</fpage><lpage>313</lpage><pub-id pub-id-type="pmid">16208694</pub-id></element-citation></ref><ref id="b64-tacg-5-001"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cooper</surname><given-names>GM</given-names></name><name><surname>Coe</surname><given-names>BP</given-names></name><name><surname>Girirajan</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>A copy number variation morbidity map of developmental delay</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>9</issue><fpage>838</fpage><lpage>846</lpage><pub-id pub-id-type="pmid">21841781</pub-id></element-citation></ref><ref id="b65-tacg-5-001"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Costain</surname><given-names>G</given-names></name><name><surname>Fung</surname><given-names>WL</given-names></name><etal></etal></person-group><article-title>Clinically detectable copy number variations in a Canadian catchment population of schizophrenia</article-title><source>J Psychiatr Res</source><year>2010</year><volume>44</volume><issue>15</issue><fpage>1005</fpage><lpage>1009</lpage><pub-id pub-id-type="pmid">20643418</pub-id></element-citation></ref><ref id="b66-tacg-5-001"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>WL</given-names></name><name><surname>McEvilly</surname><given-names>R</given-names></name><name><surname>Fong</surname><given-names>J</given-names></name><name><surname>Silversides</surname><given-names>CK</given-names></name><name><surname>Chow</surname><given-names>EWC</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome</article-title><source>Am J Psychiatry</source><year>2010</year><volume>167</volume><issue>8</issue><fpage>998</fpage><pub-id pub-id-type="pmid">20693476</pub-id></element-citation></ref><ref id="b67-tacg-5-001"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murphy</surname><given-names>KC</given-names></name><name><surname>Jones</surname><given-names>LA</given-names></name><name><surname>Owen</surname><given-names>MJ</given-names></name></person-group><article-title>High rates of schizophrenia in adults with velo-cardio-facial syndrome</article-title><source>Arch Gen Psychiatry</source><year>1999</year><volume>56</volume><issue>10</issue><fpage>940</fpage><lpage>945</lpage><pub-id pub-id-type="pmid">10530637</pub-id></element-citation></ref><ref id="b68-tacg-5-001"><label>68</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Amelsvoort</surname><given-names>T</given-names></name><name><surname>Henry</surname><given-names>J</given-names></name><name><surname>Morris</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome</article-title><source>Schizophr Res</source><year>2004</year><volume>70</volume><issue>2–3</issue><fpage>223</fpage><lpage>232</lpage><pub-id pub-id-type="pmid">15329299</pub-id></element-citation></ref><ref id="b69-tacg-5-001"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>AbdelMalik</surname><given-names>P</given-names></name><name><surname>Gheorghiu</surname><given-names>M</given-names></name><name><surname>Husted</surname><given-names>J</given-names></name><name><surname>Weksberg</surname><given-names>R</given-names></name></person-group><article-title>The schizophrenia phenotype in 22q11 deletion syndrome</article-title><source>Am J Psychiatry</source><year>2003</year><volume>160</volume><issue>9</issue><fpage>1580</fpage><lpage>1586</lpage><pub-id pub-id-type="pmid">12944331</pub-id></element-citation></ref><ref id="b70-tacg-5-001"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Watson</surname><given-names>M</given-names></name><name><surname>Young</surname><given-names>DA</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Neurocognitive profile in 22q11 deletion syndrome and schizophrenia</article-title><source>Schizophr Res</source><year>2006</year><volume>87</volume><issue>1–3</issue><fpage>270</fpage><lpage>278</lpage><pub-id pub-id-type="pmid">16753283</pub-id></element-citation></ref><ref id="b71-tacg-5-001"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stoddard</surname><given-names>J</given-names></name><name><surname>Niendam</surname><given-names>T</given-names></name><name><surname>Hendren</surname><given-names>R</given-names></name><name><surname>Carter</surname><given-names>C</given-names></name><name><surname>Simon</surname><given-names>TJ</given-names></name></person-group><article-title>Attenuated positive symptoms of psychosis in adolescents with chromosome 22q11.2 deletion syndrome</article-title><source>Schizophr Res</source><year>2010</year><volume>118</volume><issue>1–3</issue><fpage>118</fpage><lpage>121</lpage><pub-id pub-id-type="pmid">20056393</pub-id></element-citation></ref><ref id="b72-tacg-5-001"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Torres-Juan</surname><given-names>L</given-names></name><name><surname>Rosell</surname><given-names>J</given-names></name><name><surname>Sanchez-de-la-Torre</surname><given-names>M</given-names></name><name><surname>Fibla</surname><given-names>J</given-names></name><name><surname>Heine-Suner</surname><given-names>D</given-names></name></person-group><article-title>Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications</article-title><source>BMC Med Genet</source><year>2007</year><volume>8</volume><fpage>14</fpage><pub-id pub-id-type="pmid">17397557</pub-id></element-citation></ref><ref id="b73-tacg-5-001"><label>73</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name></person-group><article-title>22q11 deletion syndrome: a genetic subtype of schizophrenia</article-title><source>Biol Psychiatry</source><year>1999</year><volume>46</volume><issue>7</issue><fpage>882</fpage><lpage>891</lpage><pub-id pub-id-type="pmid">10509171</pub-id></element-citation></ref><ref id="b74-tacg-5-001"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Antshel</surname><given-names>KM</given-names></name><name><surname>Fremont</surname><given-names>W</given-names></name><name><surname>Roizen</surname><given-names>NJ</given-names></name><etal></etal></person-group><article-title>ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome</article-title><source>J Am Acad Child Adolesc Psychiatry</source><year>2006</year><volume>45</volume><issue>5</issue><fpage>596</fpage><lpage>603</lpage><pub-id pub-id-type="pmid">16670654</pub-id></element-citation></ref><ref id="b75-tacg-5-001"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Husted</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Premature death in adults with 22q11.2 deletion syndrome</article-title><source>J Med Genet</source><year>2009</year><volume>46</volume><issue>5</issue><fpage>324</fpage><lpage>330</lpage><pub-id pub-id-type="pmid">19246480</pub-id></element-citation></ref><ref id="b76-tacg-5-001"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Booij</surname><given-names>J</given-names></name><name><surname>van Amelsvoort</surname><given-names>T</given-names></name><name><surname>Boot</surname><given-names>E</given-names></name></person-group><article-title>Co-occurrence of early-onset Parkinson disease and 22q11.2 deletion syndrome: Potential role for dopamine transporter imaging</article-title><source>Am J Med Genet A</source><year>2010</year><volume>152A</volume><issue>11</issue><fpage>2937</fpage><lpage>2938</lpage><pub-id pub-id-type="pmid">20949509</pub-id></element-citation></ref><ref id="b77-tacg-5-001"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Smedt</surname><given-names>B</given-names></name><name><surname>Swillen</surname><given-names>A</given-names></name><name><surname>Verschaffel</surname><given-names>L</given-names></name><name><surname>Ghesquiere</surname><given-names>P</given-names></name></person-group><article-title>Mathematical learning disabilities in children with 22q11.2 deletion syndrome: a review</article-title><source>Dev Disabil Res Rev</source><year>2009</year><volume>15</volume><issue>1</issue><fpage>4</fpage><lpage>10</lpage><pub-id pub-id-type="pmid">19213009</pub-id></element-citation></ref><ref id="b78-tacg-5-001"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Green</surname><given-names>T</given-names></name><name><surname>Gothelf</surname><given-names>D</given-names></name><name><surname>Glaser</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome</article-title><source>J Am Acad Child Adolesc Psychiatry</source><year>2009</year><volume>48</volume><issue>11</issue><fpage>1060</fpage><lpage>1068</lpage><pub-id pub-id-type="pmid">19797984</pub-id></element-citation></ref><ref id="b79-tacg-5-001"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hercher</surname><given-names>L</given-names></name><name><surname>Bruenner</surname><given-names>G</given-names></name></person-group><article-title>Living with a child at risk for psychotic illness: the experience of parents coping with 22q11 deletion syndrome: an exploratory study</article-title><source>Am J Med Genet A</source><year>2008</year><volume>146A</volume><issue>18</issue><fpage>2355</fpage><lpage>2360</lpage><pub-id pub-id-type="pmid">18698620</pub-id></element-citation></ref><ref id="b80-tacg-5-001"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jolin</surname><given-names>EM</given-names></name><name><surname>Weller</surname><given-names>RA</given-names></name><name><surname>Jessani</surname><given-names>NR</given-names></name><name><surname>Zackai</surname><given-names>EH</given-names></name><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Weller</surname><given-names>EB</given-names></name></person-group><article-title>Affective disorders and other psychiatric diagnoses in children and adolescents with 22q11.2 Deletion Syndrome</article-title><source>J Affect Disord</source><year>2009</year><volume>119</volume><issue>1–3</issue><fpage>177</fpage><lpage>180</lpage><pub-id pub-id-type="pmid">19269692</pub-id></element-citation></ref><ref id="b81-tacg-5-001"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kapadia</surname><given-names>RK</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Recognizing a common genetic syndrome: 22q11.2 deletion syndrome</article-title><source>CMAJ</source><year>2008</year><volume>178</volume><issue>4</issue><fpage>391</fpage><lpage>393</lpage><pub-id pub-id-type="pmid">18268261</pub-id></element-citation></ref><ref id="b82-tacg-5-001"><label>82</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lawrence</surname><given-names>S</given-names></name><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Zackai</surname><given-names>E</given-names></name><name><surname>Sullivan</surname><given-names>KE</given-names></name></person-group><article-title>Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome</article-title><source>J Pediatr</source><year>2003</year><volume>143</volume><issue>2</issue><fpage>277</fpage><lpage>278</lpage><pub-id pub-id-type="pmid">12970648</pub-id></element-citation></ref><ref id="b83-tacg-5-001"><label>83</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Kirschner</surname><given-names>R</given-names></name><name><surname>Goldmuntz</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>The Philadelphia story: the 22q11.2 deletion: report on 250 patients</article-title><source>Genet Couns</source><year>1999</year><volume>10</volume><issue>1</issue><fpage>11</fpage><lpage>24</lpage><pub-id pub-id-type="pmid">10191425</pub-id></element-citation></ref><ref id="b84-tacg-5-001"><label>84</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McDonald-McGinn</surname><given-names>DM</given-names></name><name><surname>Zackai</surname><given-names>EH</given-names></name></person-group><article-title>Genetic counseling for the 22q11.2 deletion</article-title><source>Dev Disabil Res Rev</source><year>2008</year><volume>14</volume><issue>1</issue><fpage>69</fpage><lpage>74</lpage><pub-id pub-id-type="pmid">18636638</pub-id></element-citation></ref><ref id="b85-tacg-5-001"><label>85</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oskarsdottir</surname><given-names>S</given-names></name><name><surname>Persson</surname><given-names>C</given-names></name><name><surname>Eriksson</surname><given-names>BO</given-names></name><name><surname>Fasth</surname><given-names>A</given-names></name></person-group><article-title>Presenting phenotype in 100 children with the 22q11 deletion syndrome</article-title><source>Eur J Pediatr</source><year>2005</year><volume>164</volume><issue>3</issue><fpage>146</fpage><lpage>153</lpage><pub-id pub-id-type="pmid">15565286</pub-id></element-citation></ref><ref id="b86-tacg-5-001"><label>86</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ryan</surname><given-names>AK</given-names></name><name><surname>Goodship</surname><given-names>JA</given-names></name><name><surname>Wilson</surname><given-names>DI</given-names></name><etal></etal></person-group><article-title>Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study</article-title><source>J Med Genet</source><year>1997</year><volume>34</volume><issue>10</issue><fpage>798</fpage><lpage>804</lpage><pub-id pub-id-type="pmid">9350810</pub-id></element-citation></ref><ref id="b87-tacg-5-001"><label>87</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vantrappen</surname><given-names>G</given-names></name><name><surname>Devriendt</surname><given-names>K</given-names></name><name><surname>Swillen</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Presenting symptoms and clinical features in 130 patients with the velo-cardio-facial syndrome. The Leuven experience</article-title><source>Genet Couns</source><year>1999</year><volume>10</volume><issue>1</issue><fpage>3</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">10191424</pub-id></element-citation></ref><ref id="b88-tacg-5-001"><label>88</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zaleski</surname><given-names>C</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Tam</surname><given-names>K</given-names></name><name><surname>Shugar</surname><given-names>AL</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>McPherson</surname><given-names>E</given-names></name></person-group><article-title>The co-occurrence of early onset Parkinson disease and 22q11.2 deletion syndrome</article-title><source>Am J Med Genet A</source><year>2009</year><volume>149A</volume><issue>3</issue><fpage>525</fpage><lpage>528</lpage><pub-id pub-id-type="pmid">19208384</pub-id></element-citation></ref><ref id="b89-tacg-5-001"><label>89</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Husted</surname><given-names>J</given-names></name><name><surname>Weksberg</surname><given-names>R</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Postmaturity in a genetic subtype of schizophrenia</article-title><source>Acta Psychiatr Scand</source><year>2003</year><volume>108</volume><issue>4</issue><fpage>260</fpage><lpage>268</lpage><pub-id pub-id-type="pmid">12956826</pub-id></element-citation></ref><ref id="b90-tacg-5-001"><label>90</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gothelf</surname><given-names>D</given-names></name><name><surname>Eliez</surname><given-names>S</given-names></name><name><surname>Thompson</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome</article-title><source>Nat Neurosci</source><year>2005</year><volume>8</volume><issue>11</issue><fpage>1500</fpage><lpage>1502</lpage><pub-id pub-id-type="pmid">16234808</pub-id></element-citation></ref><ref id="b91-tacg-5-001"><label>91</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vorstman</surname><given-names>JA</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Ophoff</surname><given-names>RA</given-names></name><etal></etal></person-group><article-title>Association of the PIK4CA schizophrenia-susceptibility gene in adults with the 22q11.2 deletion syndrome</article-title><source>Am J Med Genet B Neuropsychiatr Genet</source><year>2009</year><volume>150B</volume><issue>3</issue><fpage>430</fpage><lpage>433</lpage><pub-id pub-id-type="pmid">18646052</pub-id></element-citation></ref><ref id="b92-tacg-5-001"><label>92</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guo</surname><given-names>T</given-names></name><name><surname>McDonald-McGinn</surname><given-names>D</given-names></name><name><surname>Blonska</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardiofacial/digeorge/22q11.2 deletion syndrome patients</article-title><source>Hum Mutat</source><year>2011</year><volume>32</volume><issue>11</issue><fpage>1278</fpage><lpage>1289</lpage><pub-id pub-id-type="pmid">21796729</pub-id></element-citation></ref><ref id="b93-tacg-5-001"><label>93</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Swaby</surname><given-names>JA</given-names></name><name><surname>Silversides</surname><given-names>CK</given-names></name><name><surname>Bekeschus</surname><given-names>SC</given-names></name><etal></etal></person-group><article-title>Complex congenital heart disease in unaffected relatives of adults with 22q11.2 deletion syndrome</article-title><source>Am J Cardiol</source><year>2011</year><volume>107</volume><issue>3</issue><fpage>466</fpage><lpage>471</lpage><pub-id pub-id-type="pmid">21257016</pub-id></element-citation></ref><ref id="b94-tacg-5-001"><label>94</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Caluseriu</surname><given-names>O</given-names></name><name><surname>Weksberg</surname><given-names>R</given-names></name><name><surname>Young</surname><given-names>DA</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name></person-group><article-title>Catechol- O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome</article-title><source>Biol Psychiatry</source><year>2007</year><volume>61</volume><issue>10</issue><fpage>1135</fpage><lpage>1140</lpage><pub-id pub-id-type="pmid">17217925</pub-id></element-citation></ref><ref id="b95-tacg-5-001"><label>95</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boot</surname><given-names>E</given-names></name><name><surname>Booij</surname><given-names>J</given-names></name><name><surname>Abeling</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia – relationship with COMT Val(1)/(1)Met polymorphism, gender and symptomatology</article-title><source>J Psychopharmacol</source><year>2011</year><volume>25</volume><issue>7</issue><fpage>888</fpage><lpage>895</lpage><pub-id pub-id-type="pmid">21447540</pub-id></element-citation></ref><ref id="b96-tacg-5-001"><label>96</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ikeda</surname><given-names>M</given-names></name><name><surname>Williams</surname><given-names>N</given-names></name><name><surname>Williams</surname><given-names>HJ</given-names></name><etal></etal></person-group><article-title>Failure to confirm association between PIK4CA and psychosis in 22q11.2 deletion syndrome</article-title><source>Am J Med Genet B Neuropsychiatr Genet</source><year>2010</year><volume>153B</volume><issue>4</issue><fpage>980</fpage><lpage>982</lpage><pub-id pub-id-type="pmid">20052689</pub-id></element-citation></ref><ref id="b97-tacg-5-001"><label>97</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Antshel</surname><given-names>KM</given-names></name><name><surname>Shprintzen</surname><given-names>R</given-names></name><name><surname>Fremont</surname><given-names>W</given-names></name><name><surname>Higgins</surname><given-names>AM</given-names></name><name><surname>Faraone</surname><given-names>SV</given-names></name><name><surname>Kates</surname><given-names>WR</given-names></name></person-group><article-title>Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: a 3-year follow-up study</article-title><source>J Am Acad Child Adolesc Psychiatry</source><year>2010</year><volume>49</volume><issue>4</issue><fpage>333</fpage><lpage>344</lpage><pub-id pub-id-type="pmid">20410726</pub-id></element-citation></ref><ref id="b98-tacg-5-001"><label>98</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gothelf</surname><given-names>D</given-names></name><name><surname>Feinstein</surname><given-names>C</given-names></name><name><surname>Thompson</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome</article-title><source>Am J Psychiatry</source><year>2007</year><volume>164</volume><issue>4</issue><fpage>663</fpage><lpage>669</lpage><pub-id pub-id-type="pmid">17403981</pub-id></element-citation></ref><ref id="b99-tacg-5-001"><label>99</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gothelf</surname><given-names>D</given-names></name><name><surname>Hoeft</surname><given-names>F</given-names></name><name><surname>Ueno</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome</article-title><source>J Psychiatr Res</source><year>2011</year><volume>45</volume><issue>3</issue><fpage>322</fpage><lpage>331</lpage><pub-id pub-id-type="pmid">20817203</pub-id></element-citation></ref><ref id="b100-tacg-5-001"><label>100</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Ho</surname><given-names>A</given-names></name><name><surname>Wei</surname><given-names>C</given-names></name><name><surname>Voormolen</surname><given-names>EH</given-names></name><name><surname>Crawley</surname><given-names>AP</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Association of schizophrenia in 22q11.2 deletion syndrome and gray matter volumetric deficits in the superior temporal gyrus</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>5</issue><fpage>522</fpage><lpage>529</lpage><pub-id pub-id-type="pmid">21362743</pub-id></element-citation></ref><ref id="b101-tacg-5-001"><label>101</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Emsley</surname><given-names>R</given-names></name><name><surname>Chiliza</surname><given-names>B</given-names></name><name><surname>Schoeman</surname><given-names>R</given-names></name></person-group><article-title>Predictors of long-term outcome in schizophrenia</article-title><source>Curr Opin Psychiatry</source><year>2008</year><volume>21</volume><issue>2</issue><fpage>173</fpage><lpage>177</lpage><pub-id pub-id-type="pmid">18332666</pub-id></element-citation></ref><ref id="b102-tacg-5-001"><label>102</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bromet</surname><given-names>EJ</given-names></name><name><surname>Kotov</surname><given-names>R</given-names></name><name><surname>Fochtmann</surname><given-names>LJ</given-names></name><etal></etal></person-group><article-title>Diagnostic shifts during the decade following first admission for psychosis</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>11</issue><fpage>1186</fpage><lpage>1194</lpage><pub-id pub-id-type="pmid">21676994</pub-id></element-citation></ref><ref id="b103-tacg-5-001"><label>103</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Werner</surname><given-names>S</given-names></name><name><surname>Stawski</surname><given-names>M</given-names></name></person-group><article-title>Knowledge, attitudes and training of professionals on dual diagnosis of intellectual disability and psychiatric disorder</article-title><source>J Intellect Disabil Res</source><year>2011</year></element-citation></ref><ref id="b104-tacg-5-001"><label>104</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Badner</surname><given-names>JA</given-names></name><name><surname>Gershon</surname><given-names>ES</given-names></name></person-group><article-title>Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia</article-title><source>Mol Psychiatry</source><year>2002</year><volume>7</volume><issue>4</issue><fpage>405</fpage><lpage>411</lpage><pub-id pub-id-type="pmid">11986984</pub-id></element-citation></ref><ref id="b105-tacg-5-001"><label>105</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lewis</surname><given-names>CM</given-names></name><name><surname>Levinson</surname><given-names>DF</given-names></name><name><surname>Wise</surname><given-names>LH</given-names></name><etal></etal></person-group><article-title>Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia</article-title><source>Am J Hum Genet</source><year>2003</year><volume>73</volume><issue>1</issue><fpage>34</fpage><lpage>48</lpage><pub-id pub-id-type="pmid">12802786</pub-id></element-citation></ref><ref id="b106-tacg-5-001"><label>106</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ng</surname><given-names>MY</given-names></name><name><surname>Levinson</surname><given-names>DF</given-names></name><name><surname>Faraone</surname><given-names>SV</given-names></name><etal></etal></person-group><article-title>Meta-analysis of 32 genome-wide linkage studies of schizophrenia</article-title><source>Mol Psychiatry</source><year>2009</year><volume>14</volume><issue>8</issue><fpage>774</fpage><lpage>785</lpage><pub-id pub-id-type="pmid">19349958</pub-id></element-citation></ref><ref id="b107-tacg-5-001"><label>107</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Owen</surname><given-names>MJ</given-names></name><name><surname>Williams</surname><given-names>NM</given-names></name><name><surname>O’Donovan</surname><given-names>MC</given-names></name></person-group><article-title>The molecular genetics of schizophrenia: new findings promise new insights</article-title><source>Mol Psychiatry</source><year>2004</year><volume>9</volume><issue>1</issue><fpage>14</fpage><lpage>27</lpage><pub-id pub-id-type="pmid">14581932</pub-id></element-citation></ref><ref id="b108-tacg-5-001"><label>108</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Waterwort</surname><given-names>DM</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Brzustowicz</surname><given-names>LM</given-names></name></person-group><article-title>Recent advances in the genetics of schizophrenia</article-title><source>Cell Mol Life Sci</source><year>2002</year><volume>59</volume><issue>2</issue><fpage>331</fpage><lpage>348</lpage><pub-id pub-id-type="pmid">11915947</pub-id></element-citation></ref><ref id="b109-tacg-5-001"><label>109</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blouin</surname><given-names>JL</given-names></name><name><surname>Dombroski</surname><given-names>BA</given-names></name><name><surname>Nath</surname><given-names>SK</given-names></name><etal></etal></person-group><article-title>Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21</article-title><source>Nat Genet</source><year>1998</year><volume>20</volume><issue>1</issue><fpage>70</fpage><lpage>73</lpage><pub-id pub-id-type="pmid">9731535</pub-id></element-citation></ref><ref id="b110-tacg-5-001"><label>110</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brzustowicz</surname><given-names>LM</given-names></name><name><surname>Honer</surname><given-names>WG</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><etal></etal></person-group><article-title>Linkage of familial schizophrenia to chromosome 13q32</article-title><source>Am J Hum Genet</source><year>1999</year><volume>65</volume><issue>4</issue><fpage>1096</fpage><lpage>1103</lpage><pub-id pub-id-type="pmid">10486329</pub-id></element-citation></ref><ref id="b111-tacg-5-001"><label>111</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brzustowicz</surname><given-names>LM</given-names></name><name><surname>Hodgkinson</surname><given-names>KA</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Honer</surname><given-names>WG</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22</article-title><source>Science</source><year>2000</year><volume>288</volume><issue>5466</issue><fpage>678</fpage><lpage>682</lpage><pub-id pub-id-type="pmid">10784452</pub-id></element-citation></ref><ref id="b112-tacg-5-001"><label>112</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ekelund</surname><given-names>J</given-names></name><name><surname>Hovatta</surname><given-names>I</given-names></name><name><surname>Parker</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Chromosome 1 loci in Finnish schizophrenia families</article-title><source>Hum Mol Genet</source><year>2001</year><volume>10</volume><issue>15</issue><fpage>1611</fpage><lpage>1617</lpage><pub-id pub-id-type="pmid">11468279</pub-id></element-citation></ref><ref id="b113-tacg-5-001"><label>113</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gurling</surname><given-names>HM</given-names></name><name><surname>Kalsi</surname><given-names>G</given-names></name><name><surname>Brynjolfson</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1- 11.23</article-title><source>Am J Hum Genet</source><year>2001</year><volume>68</volume><issue>3</issue><fpage>661</fpage><lpage>673</lpage><pub-id pub-id-type="pmid">11179014</pub-id></element-citation></ref><ref id="b114-tacg-5-001"><label>114</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Holmans</surname><given-names>PA</given-names></name><name><surname>Riley</surname><given-names>B</given-names></name><name><surname>Pulver</surname><given-names>AE</given-names></name><etal></etal></person-group><article-title>Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms</article-title><source>Mol Psychiatry</source><year>2009</year><volume>14</volume><issue>8</issue><fpage>786</fpage><lpage>795</lpage><pub-id pub-id-type="pmid">19223858</pub-id></element-citation></ref><ref id="b115-tacg-5-001"><label>115</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>MW</given-names></name><name><surname>Sham</surname><given-names>P</given-names></name><name><surname>Hwu</surname><given-names>HG</given-names></name><name><surname>Collier</surname><given-names>D</given-names></name><name><surname>Murray</surname><given-names>R</given-names></name><name><surname>Powell</surname><given-names>JF</given-names></name></person-group><article-title>Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations</article-title><source>Hum Genet</source><year>1997</year><volume>99</volume><issue>3</issue><fpage>417</fpage><lpage>420</lpage><pub-id pub-id-type="pmid">9050933</pub-id></element-citation></ref><ref id="b116-tacg-5-001"><label>116</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shaw</surname><given-names>SH</given-names></name><name><surname>Kelly</surname><given-names>M</given-names></name><name><surname>Smith</surname><given-names>AB</given-names></name><etal></etal></person-group><article-title>A genome-wide search for schizophrenia susceptibility genes</article-title><source>Am J Med Genet</source><year>1998</year><volume>81</volume><issue>5</issue><fpage>364</fpage><lpage>376</lpage><pub-id pub-id-type="pmid">9754621</pub-id></element-citation></ref><ref id="b117-tacg-5-001"><label>117</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stefansson</surname><given-names>H</given-names></name><name><surname>Sigurdsson</surname><given-names>E</given-names></name><name><surname>Steinthorsdottir</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Neuregulin 1 and susceptibility to schizophrenia</article-title><source>Am J Hum Genet</source><year>2002</year><volume>71</volume><issue>4</issue><fpage>877</fpage><lpage>892</lpage><pub-id pub-id-type="pmid">12145742</pub-id></element-citation></ref><ref id="b118-tacg-5-001"><label>118</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Straub</surname><given-names>RE</given-names></name><name><surname>MacLean</surname><given-names>CJ</given-names></name><name><surname>O’Neill</surname><given-names>FA</given-names></name><name><surname>Walsh</surname><given-names>D</given-names></name><name><surname>Kendler</surname><given-names>KS</given-names></name></person-group><article-title>Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families</article-title><source>Mol Psychiatry</source><year>1997</year><volume>2</volume><issue>2</issue><fpage>148</fpage><lpage>155</lpage><pub-id pub-id-type="pmid">9106240</pub-id></element-citation></ref><ref id="b119-tacg-5-001"><label>119</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vieland</surname><given-names>VJ</given-names></name></person-group><article-title>Thermometers: something for statistical geneticists to think about</article-title><source>Hum Hered</source><year>2006</year><volume>61</volume><issue>3</issue><fpage>144</fpage><lpage>156</lpage><pub-id pub-id-type="pmid">16770079</pub-id></element-citation></ref><ref id="b120-tacg-5-001"><label>120</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Faraone</surname><given-names>SV</given-names></name><name><surname>Hwu</surname><given-names>HG</given-names></name><name><surname>Liu</surname><given-names>CM</given-names></name><etal></etal></person-group><article-title>Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of linkage to 10q22.3</article-title><source>Am J Psychiatry</source><year>2006</year><volume>163</volume><issue>10</issue><fpage>1760</fpage><lpage>1766</lpage><pub-id pub-id-type="pmid">17012687</pub-id></element-citation></ref><ref id="b121-tacg-5-001"><label>121</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goes</surname><given-names>FS</given-names></name><name><surname>Zandi</surname><given-names>PP</given-names></name><name><surname>Miao</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33</article-title><source>Am J Psychiatry</source><year>2007</year><volume>164</volume><issue>2</issue><fpage>236</fpage><lpage>247</lpage><pub-id pub-id-type="pmid">17267786</pub-id></element-citation></ref><ref id="b122-tacg-5-001"><label>122</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Suarez</surname><given-names>BK</given-names></name><name><surname>Duan</surname><given-names>J</given-names></name><name><surname>Sanders</surname><given-names>AR</given-names></name><etal></etal></person-group><article-title>Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample</article-title><source>Am J Hum Genet</source><year>2006</year><volume>78</volume><issue>2</issue><fpage>315</fpage><lpage>333</lpage><pub-id pub-id-type="pmid">16400611</pub-id></element-citation></ref><ref id="b123-tacg-5-001"><label>123</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wratten</surname><given-names>NS</given-names></name><name><surname>Memoli</surname><given-names>H</given-names></name><name><surname>Huang</surname><given-names>Y</given-names></name><etal></etal></person-group><article-title>Identification of a schizophrenia- associated functional noncoding variant in NOS1AP</article-title><source>Am J Psychiatry</source><year>2009</year><volume>166</volume><issue>4</issue><fpage>434</fpage><lpage>441</lpage><pub-id pub-id-type="pmid">19255043</pub-id></element-citation></ref><ref id="b124-tacg-5-001"><label>124</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gershon</surname><given-names>ES</given-names></name><name><surname>Alliey-Rodriguez</surname><given-names>N</given-names></name><name><surname>Liu</surname><given-names>C</given-names></name></person-group><article-title>After GWAS: searching for genetic risk for schizophrenia and bipolar disorder</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>3</issue><fpage>253</fpage><lpage>256</lpage><pub-id pub-id-type="pmid">21285144</pub-id></element-citation></ref><ref id="b125-tacg-5-001"><label>125</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Athanasiu</surname><given-names>L</given-names></name><name><surname>Mattingsdal</surname><given-names>M</given-names></name><name><surname>Kahler</surname><given-names>AK</given-names></name><etal></etal></person-group><article-title>Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort</article-title><source>J Psychiatr Res</source><year>2010</year><volume>44</volume><issue>12</issue><fpage>748</fpage><lpage>753</lpage><pub-id pub-id-type="pmid">20185149</pub-id></element-citation></ref><ref id="b126-tacg-5-001"><label>126</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lencz</surname><given-names>T</given-names></name><name><surname>Morgan</surname><given-names>TV</given-names></name><name><surname>Athanasiou</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia</article-title><source>Mol Psychiatry</source><year>2007</year><volume>12</volume><issue>6</issue><fpage>572</fpage><lpage>580</lpage><pub-id pub-id-type="pmid">17522711</pub-id></element-citation></ref><ref id="b127-tacg-5-001"><label>127</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Need</surname><given-names>AC</given-names></name><name><surname>Ge</surname><given-names>D</given-names></name><name><surname>Weale</surname><given-names>ME</given-names></name><etal></etal></person-group><article-title>A genome-wide investigation of SNPs and CNVs in schizophrenia</article-title><source>PLoS Genet</source><year>2009</year><volume>5</volume><issue>2</issue><fpage>e1000373</fpage><pub-id pub-id-type="pmid">19197363</pub-id></element-citation></ref><ref id="b128-tacg-5-001"><label>128</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schanze</surname><given-names>D</given-names></name><name><surname>Ekici</surname><given-names>AB</given-names></name><name><surname>Gawlik</surname><given-names>M</given-names></name><name><surname>Pfuhlmann</surname><given-names>B</given-names></name><name><surname>Reis</surname><given-names>A</given-names></name><name><surname>Stober</surname><given-names>G</given-names></name></person-group><article-title>Evaluation of risk loci for schizophrenia derived from genome-wide association studies in a German population</article-title><source>Am J Med Genet B Neuropsychiatr Genet</source><year>2011</year><volume>156</volume><issue>2</issue><fpage>198</fpage><lpage>203</lpage><pub-id pub-id-type="pmid">21302348</pub-id></element-citation></ref><ref id="b129-tacg-5-001"><label>129</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sullivan</surname><given-names>PF</given-names></name><name><surname>Lin</surname><given-names>D</given-names></name><name><surname>Tzeng</surname><given-names>JY</given-names></name><etal></etal></person-group><article-title>Genomewide association for schizophrenia in the CATIE study: results of stage 1</article-title><source>Mol Psychiatry</source><year>2008</year><volume>13</volume><issue>6</issue><fpage>570</fpage><lpage>584</lpage><pub-id pub-id-type="pmid">18347602</pub-id></element-citation></ref><ref id="b130-tacg-5-001"><label>130</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’Donovan</surname><given-names>MC</given-names></name><name><surname>Craddock</surname><given-names>N</given-names></name><name><surname>Norton</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Identification of loci associated with schizophrenia by genome-wide association and followup</article-title><source>Nat Genet</source><year>2008</year><volume>40</volume><issue>9</issue><fpage>1053</fpage><lpage>1055</lpage><pub-id pub-id-type="pmid">18677311</pub-id></element-citation></ref><ref id="b131-tacg-5-001"><label>131</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Purcell</surname><given-names>SM</given-names></name><name><surname>Wray</surname><given-names>NR</given-names></name><name><surname>Stone</surname><given-names>JL</given-names></name><etal></etal></person-group><article-title>Common polygenic variation contributes to risk of schizophrenia and bipolar disorder</article-title><source>Nature</source><year>2009</year><volume>460</volume><issue>7256</issue><fpage>748</fpage><lpage>752</lpage><pub-id pub-id-type="pmid">19571811</pub-id></element-citation></ref><ref id="b132-tacg-5-001"><label>132</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rietschel</surname><given-names>M</given-names></name><name><surname>Mattheisen</surname><given-names>M</given-names></name><name><surname>Degenhardt</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe</article-title><source>Mol Psychiatry</source><year>2011</year></element-citation></ref><ref id="b133-tacg-5-001"><label>133</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ripke</surname><given-names>S</given-names></name><name><surname>Sanders</surname><given-names>AR</given-names></name><name><surname>Kendler</surname><given-names>KS</given-names></name><etal></etal></person-group><article-title>Genome-wide association study identifies five new schizophrenia loci</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>10</issue><fpage>969</fpage><lpage>976</lpage><pub-id pub-id-type="pmid">21926974</pub-id></element-citation></ref><ref id="b134-tacg-5-001"><label>134</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>J</given-names></name><name><surname>Levinson</surname><given-names>DF</given-names></name><name><surname>Duan</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Common variants on chromosome 6p22.1 are associated with schizophrenia</article-title><source>Nature</source><year>2009</year><volume>460</volume><issue>7256</issue><fpage>753</fpage><lpage>757</lpage><pub-id pub-id-type="pmid">19571809</pub-id></element-citation></ref><ref id="b135-tacg-5-001"><label>135</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stefansson</surname><given-names>H</given-names></name><name><surname>Ophoff</surname><given-names>RA</given-names></name><name><surname>Steinberg</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Common variants conferring risk of schizophrenia</article-title><source>Nature</source><year>2009</year><volume>460</volume><issue>7256</issue><fpage>744</fpage><lpage>747</lpage><pub-id pub-id-type="pmid">19571808</pub-id></element-citation></ref><ref id="b136-tacg-5-001"><label>136</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yamada</surname><given-names>K</given-names></name><name><surname>Iwayama</surname><given-names>Y</given-names></name><name><surname>Hattori</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Genome-wide association study of schizophrenia in Japanese population</article-title><source>PLoS One</source><year>2011</year><volume>6</volume><issue>6</issue><fpage>e20468</fpage><pub-id pub-id-type="pmid">21674006</pub-id></element-citation></ref><ref id="b137-tacg-5-001"><label>137</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yue</surname><given-names>WH</given-names></name><name><surname>Wang</surname><given-names>HF</given-names></name><name><surname>Sun</surname><given-names>LD</given-names></name><etal></etal></person-group><article-title>Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>12</issue><fpage>1228</fpage><lpage>1231</lpage><pub-id pub-id-type="pmid">22037552</pub-id></element-citation></ref><ref id="b138-tacg-5-001"><label>138</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Crowe</surname><given-names>RR</given-names></name><name><surname>Thompson</surname><given-names>JS</given-names></name><name><surname>Flink</surname><given-names>R</given-names></name><name><surname>Weinberger</surname><given-names>B</given-names></name></person-group><article-title>HLA antigens and schizophrenia</article-title><source>Arch Gen Psychiatry</source><year>1979</year><volume>36</volume><issue>2</issue><fpage>231</fpage><lpage>233</lpage><pub-id pub-id-type="pmid">420545</pub-id></element-citation></ref><ref id="b139-tacg-5-001"><label>139</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eberhard</surname><given-names>G</given-names></name><name><surname>Franzen</surname><given-names>G</given-names></name><name><surname>Low</surname><given-names>B</given-names></name></person-group><article-title>Schizophrenia susceptibility and HL-A antigen</article-title><source>Neuropsychobiology</source><year>1975</year><volume>1</volume><issue>4</issue><fpage>211</fpage><lpage>217</lpage><pub-id pub-id-type="pmid">1226230</pub-id></element-citation></ref><ref id="b140-tacg-5-001"><label>140</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>Z</given-names></name><name><surname>Xu</surname><given-names>Q</given-names></name><etal></etal></person-group><article-title>Common variants on 8p12 and 1q24.2 confer risk of schizophrenia</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>12</issue><fpage>1224</fpage><lpage>1227</lpage><pub-id pub-id-type="pmid">22037555</pub-id></element-citation></ref><ref id="b141-tacg-5-001"><label>141</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Steinberg</surname><given-names>S</given-names></name><name><surname>de Jong</surname><given-names>S</given-names></name><name><surname>Andreassen</surname><given-names>OA</given-names></name><etal></etal></person-group><article-title>Common variants at VRK2 and TCF4 conferring risk of schizophrenia</article-title><source>Hum Mol Genet</source><year>2011</year><volume>20</volume><issue>20</issue><fpage>4076</fpage><lpage>4081</lpage><pub-id pub-id-type="pmid">21791550</pub-id></element-citation></ref><ref id="b142-tacg-5-001"><label>142</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>KS</given-names></name><name><surname>Liu</surname><given-names>XF</given-names></name><name><surname>Aragam</surname><given-names>N</given-names></name></person-group><article-title>A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder</article-title><source>Schizophr Res</source><year>2010</year><volume>124</volume><issue>1–3</issue><fpage>192</fpage><lpage>199</lpage><pub-id pub-id-type="pmid">20889312</pub-id></element-citation></ref><ref id="b143-tacg-5-001"><label>143</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Williams</surname><given-names>HJ</given-names></name><name><surname>Norton</surname><given-names>N</given-names></name><name><surname>Dwyer</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder</article-title><source>Mol Psychiatry</source><year>2011</year><volume>16</volume><issue>4</issue><fpage>429</fpage><lpage>441</lpage><pub-id pub-id-type="pmid">20368704</pub-id></element-citation></ref><ref id="b144-tacg-5-001"><label>144</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Glessner</surname><given-names>JT</given-names></name><name><surname>Reilly</surname><given-names>MP</given-names></name><name><surname>Kim</surname><given-names>CE</given-names></name><etal></etal></person-group><article-title>Strong synaptic transmission impact by copy number variations in schizophrenia</article-title><source>Proc Natl Acad Sci U S A</source><year>2010</year><volume>107</volume><issue>23</issue><fpage>10584</fpage><lpage>10589</lpage><pub-id pub-id-type="pmid">20489179</pub-id></element-citation></ref><ref id="b145-tacg-5-001"><label>145</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arranz</surname><given-names>MJ</given-names></name><name><surname>Rivera</surname><given-names>M</given-names></name><name><surname>Munro</surname><given-names>JC</given-names></name></person-group><article-title>Pharmacogenetics of response to antipsychotics in patients with schizophrenia</article-title><source>CNS Drugs</source><year>2011</year><volume>25</volume><issue>11</issue><fpage>933</fpage><lpage>969</lpage><pub-id pub-id-type="pmid">22054119</pub-id></element-citation></ref><ref id="b146-tacg-5-001"><label>146</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cacabelos</surname><given-names>R</given-names></name><name><surname>Hashimoto</surname><given-names>R</given-names></name><name><surname>Takeda</surname><given-names>M</given-names></name></person-group><article-title>Pharmacogenomics of antipsychotics efficacy for schizophrenia</article-title><source>Psychiatry Clin Neurosci</source><year>2011</year><volume>65</volume><issue>1</issue><fpage>3</fpage><lpage>19</lpage><pub-id pub-id-type="pmid">21265934</pub-id></element-citation></ref><ref id="b147-tacg-5-001"><label>147</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hodgkinson</surname><given-names>KA</given-names></name><name><surname>Murphy</surname><given-names>J</given-names></name><name><surname>O’Neill</surname><given-names>S</given-names></name><name><surname>Brzustowicz</surname><given-names>L</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Genetic counselling for schizophrenia in the era of molecular genetics</article-title><source>Can J Psychiatry</source><year>2001</year><volume>46</volume><issue>2</issue><fpage>123</fpage><lpage>130</lpage><pub-id pub-id-type="pmid">11280080</pub-id></element-citation></ref><ref id="b148-tacg-5-001"><label>148</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Allen</surname><given-names>NC</given-names></name><name><surname>Bagade</surname><given-names>S</given-names></name><name><surname>McQueen</surname><given-names>MB</given-names></name><etal></etal></person-group><article-title>Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database</article-title><source>Nat Genet</source><year>2008</year><volume>40</volume><issue>7</issue><fpage>827</fpage><lpage>834</lpage><pub-id pub-id-type="pmid">18583979</pub-id></element-citation></ref><ref id="b149-tacg-5-001"><label>149</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Girard</surname><given-names>SL</given-names></name><name><surname>Gauthier</surname><given-names>J</given-names></name><name><surname>Noreau</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Increased exonic de novo mutation rate in individuals with schizophrenia</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>9</issue><fpage>860</fpage><lpage>863</lpage><pub-id pub-id-type="pmid">21743468</pub-id></element-citation></ref><ref id="b150-tacg-5-001"><label>150</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>B</given-names></name><name><surname>Roos</surname><given-names>JL</given-names></name><name><surname>Dexheimer</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Exome sequencing supports a de novo mutational paradigm for schizophrenia</article-title><source>Nat Genet</source><year>2011</year><volume>43</volume><issue>9</issue><fpage>864</fpage><lpage>868</lpage><pub-id pub-id-type="pmid">21822266</pub-id></element-citation></ref><ref id="b151-tacg-5-001"><label>151</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cook</surname><given-names>EH</given-names><suffix>Jr</suffix></name><name><surname>Scherer</surname><given-names>SW</given-names></name></person-group><article-title>Copy-number variations associated with neuropsychiatric conditions</article-title><source>Nature</source><year>2008</year><volume>455</volume><issue>7215</issue><fpage>919</fpage><lpage>923</lpage><pub-id pub-id-type="pmid">18923514</pub-id></element-citation></ref><ref id="b152-tacg-5-001"><label>152</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iafrate</surname><given-names>AJ</given-names></name><name><surname>Feuk</surname><given-names>L</given-names></name><name><surname>Rivera</surname><given-names>MN</given-names></name><etal></etal></person-group><article-title>Detection of large-scale variation in the human genome</article-title><source>Nat Genet</source><year>2004</year><volume>36</volume><issue>9</issue><fpage>949</fpage><lpage>951</lpage><pub-id pub-id-type="pmid">15286789</pub-id></element-citation></ref><ref id="b153-tacg-5-001"><label>153</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>C</given-names></name><name><surname>Scherer</surname><given-names>SW</given-names></name></person-group><article-title>The clinical context of copy number variation in the human genome</article-title><source>Expert Rev Mol Med</source><year>2010</year><volume>12</volume><fpage>e8</fpage><pub-id pub-id-type="pmid">20211047</pub-id></element-citation></ref><ref id="b154-tacg-5-001"><label>154</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Redon</surname><given-names>R</given-names></name><name><surname>Ishikawa</surname><given-names>S</given-names></name><name><surname>Fitch</surname><given-names>KR</given-names></name><etal></etal></person-group><article-title>Global variation in copy number in the human genome</article-title><source>Nature</source><year>2006</year><volume>444</volume><issue>7118</issue><fpage>444</fpage><lpage>454</lpage><pub-id pub-id-type="pmid">17122850</pub-id></element-citation></ref><ref id="b155-tacg-5-001"><label>155</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sebat</surname><given-names>J</given-names></name><name><surname>Lakshmi</surname><given-names>B</given-names></name><name><surname>Troge</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Large-scale copy number polymorphism in the human genome</article-title><source>Science</source><year>2004</year><volume>305</volume><issue>5683</issue><fpage>525</fpage><lpage>528</lpage><pub-id pub-id-type="pmid">15273396</pub-id></element-citation></ref><ref id="b156-tacg-5-001"><label>156</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Chromosomal aberrations and schizophrenia. Autosomes</article-title><source>Br J Psychiatry</source><year>1992</year><volume>161</volume><fpage>323</fpage><lpage>334</lpage><pub-id pub-id-type="pmid">1393302</pub-id></element-citation></ref><ref id="b157-tacg-5-001"><label>157</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ingason</surname><given-names>A</given-names></name><name><surname>Kirov</surname><given-names>G</given-names></name><name><surname>Giegling</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>4</issue><fpage>408</fpage><lpage>417</lpage><pub-id pub-id-type="pmid">21324950</pub-id></element-citation></ref><ref id="b158-tacg-5-001"><label>158</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grozeva</surname><given-names>D</given-names></name><name><surname>Kirov</surname><given-names>G</given-names></name><name><surname>Ivanov</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia</article-title><source>Arch Gen Psychiatry</source><year>2010</year><volume>67</volume><issue>4</issue><fpage>318</fpage><lpage>327</lpage><pub-id pub-id-type="pmid">20368508</pub-id></element-citation></ref><ref id="b159-tacg-5-001"><label>159</label><element-citation publication-type="journal"><collab>International Schizophrenia Consortium</collab><article-title>Rare chromosomal deletions and duplications increase risk of schizophrenia</article-title><source>Nature</source><year>2008</year><volume>455</volume><issue>7210</issue><fpage>237</fpage><lpage>241</lpage><pub-id pub-id-type="pmid">18668038</pub-id></element-citation></ref><ref id="b160-tacg-5-001"><label>160</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kirov</surname><given-names>G</given-names></name><name><surname>Grozeva</surname><given-names>D</given-names></name><name><surname>Norton</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Support for the involvement of large copy number variants in the pathogenesis of schizophrenia</article-title><source>Hum Mol Genet</source><year>2009</year><volume>18</volume><issue>8</issue><fpage>1497</fpage><lpage>1503</lpage><pub-id pub-id-type="pmid">19181681</pub-id></element-citation></ref><ref id="b161-tacg-5-001"><label>161</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kirov</surname><given-names>G</given-names></name><name><surname>Pocklington</surname><given-names>AJ</given-names></name><name><surname>Holmans</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia</article-title><source>Mol Psychiatry</source><year>2012</year><volume>17</volume><issue>2</issue><fpage>142</fpage><lpage>153</lpage><pub-id pub-id-type="pmid">22083728</pub-id></element-citation></ref><ref id="b162-tacg-5-001"><label>162</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magri</surname><given-names>C</given-names></name><name><surname>Sacchetti</surname><given-names>E</given-names></name><name><surname>Traversa</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>New copy number variations in schizophrenia</article-title><source>PLoS One</source><year>2010</year><volume>5</volume><issue>10</issue><fpage>e13422</fpage><pub-id pub-id-type="pmid">20967226</pub-id></element-citation></ref><ref id="b163-tacg-5-001"><label>163</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Melhem</surname><given-names>N</given-names></name><name><surname>Middleton</surname><given-names>F</given-names></name><name><surname>McFadden</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Copy number variants for schizophrenia and related psychotic disorders in oceanic palau: risk and transmission in extended pedigrees</article-title><source>Biol Psychiatry</source><year>2011</year><volume>70</volume><issue>12</issue><fpage>1115</fpage><lpage>1121</lpage><pub-id pub-id-type="pmid">21982423</pub-id></element-citation></ref><ref id="b164-tacg-5-001"><label>164</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stefansson</surname><given-names>H</given-names></name><name><surname>Rujescu</surname><given-names>D</given-names></name><name><surname>Cichon</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Large recurrent microdeletions associated with schizophrenia</article-title><source>Nature</source><year>2008</year><volume>455</volume><issue>7210</issue><fpage>232</fpage><lpage>236</lpage><pub-id pub-id-type="pmid">18668039</pub-id></element-citation></ref><ref id="b165-tacg-5-001"><label>165</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moreno-De-Luca</surname><given-names>D</given-names></name><name><surname>Mulle</surname><given-names>JG</given-names></name><name><surname>Kaminsky</surname><given-names>EB</given-names></name><etal></etal></person-group><article-title>Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia</article-title><source>Am J Hum Genet</source><year>2010</year><volume>87</volume><issue>5</issue><fpage>618</fpage><lpage>630</lpage><pub-id pub-id-type="pmid">21055719</pub-id></element-citation></ref><ref id="b166-tacg-5-001"><label>166</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Levinson</surname><given-names>DF</given-names></name><name><surname>Duan</surname><given-names>J</given-names></name><name><surname>Oh</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>3</issue><fpage>302</fpage><lpage>316</lpage><pub-id pub-id-type="pmid">21285140</pub-id></element-citation></ref><ref id="b167-tacg-5-001"><label>167</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ingason</surname><given-names>A</given-names></name><name><surname>Rujescu</surname><given-names>D</given-names></name><name><surname>Cichon</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Copy number variations of chromosome 16p13.1 region associated with schizophrenia</article-title><source>Mol Psychiatry</source><year>2011</year><volume>16</volume><issue>1</issue><fpage>17</fpage><lpage>25</lpage><pub-id pub-id-type="pmid">19786961</pub-id></element-citation></ref><ref id="b168-tacg-5-001"><label>168</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brunetti-Pierri</surname><given-names>N</given-names></name><name><surname>Berg</surname><given-names>JS</given-names></name><name><surname>Scaglia</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities</article-title><source>Nat Genet</source><year>2008</year><volume>40</volume><issue>12</issue><fpage>1466</fpage><lpage>1471</lpage><pub-id pub-id-type="pmid">19029900</pub-id></element-citation></ref><ref id="b169-tacg-5-001"><label>169</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Doornbos</surname><given-names>M</given-names></name><name><surname>Sikkema-Raddatz</surname><given-names>B</given-names></name><name><surname>Ruijvenkamp</surname><given-names>CA</given-names></name><etal></etal></person-group><article-title>Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances</article-title><source>Eur J Med Genet</source><year>2009</year><volume>52</volume><issue>2–3</issue><fpage>108</fpage><lpage>115</lpage><pub-id pub-id-type="pmid">19328872</pub-id></element-citation></ref><ref id="b170-tacg-5-001"><label>170</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greenway</surname><given-names>SC</given-names></name><name><surname>Pereira</surname><given-names>AC</given-names></name><name><surname>Lin</surname><given-names>JC</given-names></name><etal></etal></person-group><article-title>De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot</article-title><source>Nat Genet</source><year>2009</year><volume>41</volume><issue>8</issue><fpage>931</fpage><lpage>935</lpage><pub-id pub-id-type="pmid">19597493</pub-id></element-citation></ref><ref id="b171-tacg-5-001"><label>171</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hannes</surname><given-names>FD</given-names></name><name><surname>Sharp</surname><given-names>AJ</given-names></name><name><surname>Mefford</surname><given-names>HC</given-names></name><etal></etal></person-group><article-title>Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant</article-title><source>J Med Genet</source><year>2009</year><volume>46</volume><issue>4</issue><fpage>223</fpage><lpage>232</lpage><pub-id pub-id-type="pmid">18550696</pub-id></element-citation></ref><ref id="b172-tacg-5-001"><label>172</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harvard</surname><given-names>C</given-names></name><name><surname>Strong</surname><given-names>E</given-names></name><name><surname>Mercier</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Understanding the impact of 1q21.1 copy number variant</article-title><source>Orphanet J Rare Dis</source><year>2011</year><volume>6</volume><fpage>54</fpage><pub-id pub-id-type="pmid">21824431</pub-id></element-citation></ref><ref id="b173-tacg-5-001"><label>173</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Kovel</surname><given-names>CG</given-names></name><name><surname>Trucks</surname><given-names>H</given-names></name><name><surname>Helbig</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies</article-title><source>Brain</source><year>2010</year><volume>133</volume><issue>Pt 1</issue><fpage>23</fpage><lpage>32</lpage><pub-id pub-id-type="pmid">19843651</pub-id></element-citation></ref><ref id="b174-tacg-5-001"><label>174</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Clauin</surname><given-names>S</given-names></name><name><surname>Sharp</surname><given-names>AJ</given-names></name><etal></etal></person-group><article-title>Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy</article-title><source>Am J Hum Genet</source><year>2007</year><volume>81</volume><issue>5</issue><fpage>1057</fpage><lpage>1069</lpage><pub-id pub-id-type="pmid">17924346</pub-id></element-citation></ref><ref id="b175-tacg-5-001"><label>175</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Sharp</surname><given-names>AJ</given-names></name><name><surname>Baker</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes</article-title><source>N Engl J Med</source><year>2008</year><volume>359</volume><issue>16</issue><fpage>1685</fpage><lpage>1699</lpage><pub-id pub-id-type="pmid">18784092</pub-id></element-citation></ref><ref id="b176-tacg-5-001"><label>176</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Cooper</surname><given-names>GM</given-names></name><name><surname>Zerr</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease</article-title><source>Genome Res</source><year>2009</year><volume>19</volume><issue>9</issue><fpage>1579</fpage><lpage>1585</lpage><pub-id pub-id-type="pmid">19506092</pub-id></element-citation></ref><ref id="b177-tacg-5-001"><label>177</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagamani</surname><given-names>SC</given-names></name><name><surname>Erez</surname><given-names>A</given-names></name><name><surname>Shen</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12</article-title><source>Eur J Hum Genet</source><year>2010</year><volume>18</volume><issue>3</issue><fpage>278</fpage><lpage>284</lpage><pub-id pub-id-type="pmid">19844256</pub-id></element-citation></ref><ref id="b178-tacg-5-001"><label>178</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ullmann</surname><given-names>R</given-names></name><name><surname>Turner</surname><given-names>G</given-names></name><name><surname>Kirchhoff</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation</article-title><source>Hum Mutat</source><year>2007</year><volume>28</volume><issue>7</issue><fpage>674</fpage><lpage>682</lpage><pub-id pub-id-type="pmid">17480035</pub-id></element-citation></ref><ref id="b179-tacg-5-001"><label>179</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Williams</surname><given-names>NM</given-names></name><name><surname>Zaharieva</surname><given-names>I</given-names></name><name><surname>Martin</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis</article-title><source>Lancet</source><year>2010</year><volume>376</volume><issue>9750</issue><fpage>1401</fpage><lpage>1408</lpage><pub-id pub-id-type="pmid">20888040</pub-id></element-citation></ref><ref id="b180-tacg-5-001"><label>180</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Parental origin, DNA structure, and the schizophrenia spectrum</article-title><source>Am J Psychiatry</source><year>2011</year><volume>168</volume><issue>4</issue><fpage>350</fpage><lpage>353</lpage><pub-id pub-id-type="pmid">21474594</pub-id></element-citation></ref><ref id="b181-tacg-5-001"><label>181</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Horowitz</surname><given-names>A</given-names></name><name><surname>Shifman</surname><given-names>S</given-names></name><name><surname>Rivlin</surname><given-names>N</given-names></name><name><surname>Pisante</surname><given-names>A</given-names></name><name><surname>Darvasi</surname><given-names>A</given-names></name></person-group><article-title>A survey of the 22q11 microdeletion in a large cohort of schizophrenia patients</article-title><source>Schizophr Res</source><year>2005</year><volume>73</volume><issue>2–3</issue><fpage>263</fpage><lpage>267</lpage><pub-id pub-id-type="pmid">15653270</pub-id></element-citation></ref><ref id="b182-tacg-5-001"><label>182</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walsh</surname><given-names>T</given-names></name><name><surname>McClellan</surname><given-names>JM</given-names></name><name><surname>McCarthy</surname><given-names>SE</given-names></name><etal></etal></person-group><article-title>Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia</article-title><source>Science</source><year>2008</year><volume>320</volume><issue>5875</issue><fpage>539</fpage><lpage>543</lpage><pub-id pub-id-type="pmid">18369103</pub-id></element-citation></ref><ref id="b183-tacg-5-001"><label>183</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sporn</surname><given-names>A</given-names></name><name><surname>Addington</surname><given-names>A</given-names></name><name><surname>Reiss</surname><given-names>AL</given-names></name><etal></etal></person-group><article-title>22q11 deletion syndrome in childhood onset schizophrenia: an update</article-title><source>Mol Psychiatry</source><year>2004</year><volume>9</volume><issue>3</issue><fpage>225</fpage><lpage>226</lpage><pub-id pub-id-type="pmid">14699434</pub-id></element-citation></ref><ref id="b184-tacg-5-001"><label>184</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rapoport</surname><given-names>JL</given-names></name><name><surname>Addington</surname><given-names>AM</given-names></name><name><surname>Frangou</surname><given-names>S</given-names></name><name><surname>Psych</surname><given-names>MR</given-names></name></person-group><article-title>The neurodevelopmental model of schizophrenia: update 2005</article-title><source>Mol Psychiatry</source><year>2005</year><volume>10</volume><issue>5</issue><fpage>434</fpage><lpage>449</lpage><pub-id pub-id-type="pmid">15700048</pub-id></element-citation></ref><ref id="b185-tacg-5-001"><label>185</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Girirajan</surname><given-names>S</given-names></name><name><surname>Eichler</surname><given-names>EE</given-names></name></person-group><article-title>Phenotypic variability and genetic susceptibility to genomic disorders</article-title><source>Hum Mol Genet</source><year>2010</year><volume>19</volume><issue>R2</issue><fpage>R176</fpage><lpage>R187</lpage><pub-id pub-id-type="pmid">20807775</pub-id></element-citation></ref><ref id="b186-tacg-5-001"><label>186</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Costain</surname><given-names>G</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Ray</surname><given-names>PN</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Caregiver and adult patient perspectives on the importance of a diagnosis of 22q11.2 deletion syndrome</article-title><source>J Intellect Disabil Res</source><year>2011</year></element-citation></ref><ref id="b187-tacg-5-001"><label>187</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hodgkinson</surname><given-names>K</given-names></name><name><surname>Pullman</surname><given-names>D</given-names></name></person-group><article-title>Duty to warn and genetic disease</article-title><source>Can J Cardiovasc Nurs</source><year>2010</year><volume>20</volume><issue>1</issue><fpage>12</fpage><lpage>15</lpage><pub-id pub-id-type="pmid">20301857</pub-id></element-citation></ref><ref id="b188-tacg-5-001"><label>188</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Piggins</surname><given-names>HD</given-names></name></person-group><article-title>Schizophrenia: zooming in on a gene</article-title><source>Nature</source><year>2011</year><volume>471</volume><issue>7339</issue><fpage>455</fpage><lpage>456</lpage><pub-id pub-id-type="pmid">21430769</pub-id></element-citation></ref><ref id="b189-tacg-5-001"><label>189</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Green</surname><given-names>ED</given-names></name><name><surname>Guyer</surname><given-names>MS</given-names></name></person-group><article-title>Charting a course for genomic medicine from base pairs to bedside</article-title><source>Nature</source><year>2011</year><volume>470</volume><issue>7333</issue><fpage>204</fpage><lpage>213</lpage><pub-id pub-id-type="pmid">21307933</pub-id></element-citation></ref><ref id="b190-tacg-5-001"><label>190</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Scherer</surname><given-names>SW</given-names></name><name><surname>Dawson</surname><given-names>G</given-names></name></person-group><article-title>Risk factors for autism: translating genomic discoveries into diagnostics</article-title><source>Hum Genet</source><year>2011</year><volume>130</volume><issue>1</issue><fpage>123</fpage><lpage>148</lpage><pub-id pub-id-type="pmid">21701786</pub-id></element-citation></ref><ref id="b191-tacg-5-001"><label>191</label><element-citation publication-type="webpage"><article-title>Family history and BRCA 1/2 testing for identifying women at risk for inherited breast/ovarian cancer: AACE review</article-title><comment><ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/genomics/gtesting/ACCE/fbr.htm">http://www.cdc.gov/genomics/gtesting/ACCE/fbr.htm</ext-link></comment></element-citation></ref><ref id="b192-tacg-5-001"><label>192</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>FA</given-names></name><name><surname>Hayeems</surname><given-names>RZ</given-names></name><name><surname>Bytautas</surname><given-names>JP</given-names></name></person-group><article-title>What is a meaningful result? Disclosing the results of genomic research in autism to research participants</article-title><source>Eur J Hum Genet</source><year>2010</year><volume>18</volume><issue>8</issue><fpage>867</fpage><lpage>871</lpage><pub-id pub-id-type="pmid">20234389</pub-id></element-citation></ref><ref id="b193-tacg-5-001"><label>193</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bassett</surname><given-names>AS</given-names></name><name><surname>Bury</surname><given-names>A</given-names></name><name><surname>Hodgkinson</surname><given-names>KA</given-names></name><name><surname>Honer</surname><given-names>WG</given-names></name></person-group><article-title>Reproductive fitness in familial schizophrenia</article-title><source>Schizophr Res</source><year>1996</year><volume>21</volume><issue>3</issue><fpage>151</fpage><lpage>160</lpage><pub-id pub-id-type="pmid">8885043</pub-id></element-citation></ref><ref id="b194-tacg-5-001"><label>194</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bundy</surname><given-names>H</given-names></name><name><surname>Stahl</surname><given-names>D</given-names></name><name><surname>MacCabe</surname><given-names>JH</given-names></name></person-group><article-title>A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives</article-title><source>Acta Psychiatr Scand</source><year>2011</year><volume>123</volume><issue>2</issue><fpage>98</fpage><lpage>106</lpage><pub-id pub-id-type="pmid">20958271</pub-id></element-citation></ref><ref id="b195-tacg-5-001"><label>195</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mitchell</surname><given-names>PB</given-names></name><name><surname>Meiser</surname><given-names>B</given-names></name><name><surname>Wilde</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Predictive and diagnostic genetic testing in psychiatry</article-title><source>Clin Lab Med</source><year>2010</year><volume>30</volume><issue>4</issue><fpage>829</fpage><lpage>846</lpage><pub-id pub-id-type="pmid">20832655</pub-id></element-citation></ref><ref id="b196-tacg-5-001"><label>196</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tsuang</surname><given-names>DW</given-names></name><name><surname>Faraone</surname><given-names>SV</given-names></name><name><surname>Tsuang</surname><given-names>MT</given-names></name></person-group><article-title>Genetic counseling for psychiatric disorders</article-title><source>Curr Psychiatry Rep</source><year>2001</year><volume>3</volume><issue>2</issue><fpage>138</fpage><lpage>143</lpage><pub-id pub-id-type="pmid">11276409</pub-id></element-citation></ref><ref id="b197-tacg-5-001"><label>197</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feret</surname><given-names>H</given-names></name><name><surname>Conway</surname><given-names>L</given-names></name><name><surname>Austin</surname><given-names>JC</given-names></name></person-group><article-title>Genetic counselors’ attitudes towards individuals with schizophrenia: desire for social distance and endorsement of stereotypes</article-title><source>Patient Educ Couns</source><year>2011</year><volume>82</volume><issue>1</issue><fpage>69</fpage><lpage>73</lpage><pub-id pub-id-type="pmid">20211537</pub-id></element-citation></ref><ref id="b198-tacg-5-001"><label>198</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Monaco</surname><given-names>LC</given-names></name><name><surname>Conway</surname><given-names>L</given-names></name><name><surname>Valverde</surname><given-names>K</given-names></name><name><surname>Austin</surname><given-names>JC</given-names></name></person-group><article-title>Exploring genetic counselors’ perceptions of and attitudes towards schizophrenia</article-title><source>Public Health Genomics</source><year>2010</year><volume>13</volume><issue>1</issue><fpage>21</fpage><lpage>26</lpage><pub-id pub-id-type="pmid">19321939</pub-id></element-citation></ref><ref id="b199-tacg-5-001"><label>199</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Finucane</surname><given-names>B</given-names></name></person-group><article-title>Genetic counseling for women with intellectual disabilities</article-title><person-group person-group-type="editor"><name><surname>LeRoy</surname><given-names>BS</given-names></name><name><surname>Veach</surname><given-names>PM</given-names></name><name><surname>Bartels</surname><given-names>DM</given-names></name></person-group><source>Genetic Counseling Practice: Advanced Concepts and Skills</source><publisher-loc>Hoboken</publisher-loc><publisher-name>Wiley-Blackwell</publisher-name><year>2010</year><fpage>470</fpage><lpage>507</lpage></element-citation></ref><ref id="b200-tacg-5-001"><label>200</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Taylor</surname><given-names>MR</given-names></name><name><surname>Edwards</surname><given-names>JG</given-names></name><name><surname>Ku</surname><given-names>L</given-names></name></person-group><article-title>Lost in transition: challenges in the expanding field of adult genetics</article-title><source>Am J Med Genet C Semin Med Genet</source><year>2006</year><volume>142C</volume><issue>4</issue><fpage>294</fpage><lpage>303</lpage><pub-id pub-id-type="pmid">17024669</pub-id></element-citation></ref><ref id="b201-tacg-5-001"><label>201</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Farwig</surname><given-names>K</given-names></name><name><surname>Harmon</surname><given-names>AG</given-names></name><name><surname>Fontana</surname><given-names>KM</given-names></name><name><surname>Mervis</surname><given-names>CB</given-names></name><name><surname>Morris</surname><given-names>CA</given-names></name></person-group><article-title>Genetic counseling of adults with Williams syndrome: a first study</article-title><source>Am J Med Genet C Semin Med Genet</source><year>2010</year><volume>154C</volume><issue>2</issue><fpage>307</fpage><lpage>315</lpage><pub-id pub-id-type="pmid">20425790</pub-id></element-citation></ref><ref id="b202-tacg-5-001"><label>202</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>C</given-names></name><name><surname>Iafrate</surname><given-names>AJ</given-names></name><name><surname>Brothman</surname><given-names>AR</given-names></name></person-group><article-title>Copy number variations and clinical cytogenetic diagnosis of constitutional disorders</article-title><source>Nat Genet</source><year>2007</year><volume>39</volume><issue>7 Suppl</issue><fpage>S48</fpage><lpage>S54</lpage><pub-id pub-id-type="pmid">17597782</pub-id></element-citation></ref><ref id="b203-tacg-5-001"><label>203</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Austin</surname><given-names>JC</given-names></name><name><surname>Peay</surname><given-names>HL</given-names></name></person-group><article-title>Applications and limitations of empiric data in provision of recurrence risks for schizophrenia: a practical review for healthcare professionals providing clinical psychiatric genetics consultations</article-title><source>Clin Genet</source><year>2006</year><volume>70</volume><issue>3</issue><fpage>177</fpage><lpage>187</lpage><pub-id pub-id-type="pmid">16922717</pub-id></element-citation></ref><ref id="b204-tacg-5-001"><label>204</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Peay</surname><given-names>HL</given-names></name><name><surname>Austin</surname><given-names>JC</given-names></name></person-group><source>How to Talk with Families About Genetics and Psychiatric Illness</source><publisher-loc>New York</publisher-loc><publisher-name>WW Norton and Company</publisher-name><year>2011</year></element-citation></ref><ref id="b205-tacg-5-001"><label>205</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Simpson</surname><given-names>SA</given-names></name><name><surname>Besson</surname><given-names>J</given-names></name><name><surname>Alexander</surname><given-names>D</given-names></name><name><surname>Allan</surname><given-names>K</given-names></name><name><surname>Johnston</surname><given-names>AW</given-names></name></person-group><article-title>One hundred requests for predictive testing for Huntington’s disease</article-title><source>Clin Genet</source><year>1992</year><volume>41</volume><issue>6</issue><fpage>326</fpage><lpage>330</lpage><pub-id pub-id-type="pmid">1535837</pub-id></element-citation></ref><ref id="b206-tacg-5-001"><label>206</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tyler</surname><given-names>A</given-names></name><name><surname>Morris</surname><given-names>M</given-names></name><name><surname>Lazarou</surname><given-names>L</given-names></name><name><surname>Meredith</surname><given-names>L</given-names></name><name><surname>Myring</surname><given-names>J</given-names></name><name><surname>Harper</surname><given-names>P</given-names></name></person-group><article-title>Presymptomatic testing for Huntington’s disease in Wales 1987–1990</article-title><source>Br J Psychiatry</source><year>1992</year><volume>161</volume><fpage>481</fpage><lpage>488</lpage><pub-id pub-id-type="pmid">1393334</pub-id></element-citation></ref><ref id="b207-tacg-5-001"><label>207</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>B</given-names></name><name><surname>Woodroffe</surname><given-names>A</given-names></name><name><surname>Rodriguez-Murillo</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans</article-title><source>Proc Natl Acad Sci U S A</source><year>2009</year><volume>106</volume><issue>39</issue><fpage>16746</fpage><lpage>16751</lpage><pub-id pub-id-type="pmid">19805367</pub-id></element-citation></ref><ref id="b208-tacg-5-001"><label>208</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Chalabi</surname><given-names>A</given-names></name><name><surname>Lewis</surname><given-names>CM</given-names></name></person-group><article-title>Modelling the effects of penetrance and family size on rates of sporadic and familial disease</article-title><source>Hum Hered</source><year>2011</year><volume>71</volume><issue>4</issue><fpage>281</fpage><lpage>288</lpage><pub-id pub-id-type="pmid">21846995</pub-id></element-citation></ref><ref id="b209-tacg-5-001"><label>209</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Visscher</surname><given-names>PM</given-names></name><name><surname>Wray</surname><given-names>NR</given-names></name></person-group><article-title>Sporadic cases are the norm for complex disease</article-title><source>Eur J Hum Genet</source><year>2010</year><volume>18</volume><issue>9</issue><fpage>1039</fpage><lpage>1043</lpage><pub-id pub-id-type="pmid">19826454</pub-id></element-citation></ref><ref id="b210-tacg-5-001"><label>210</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shulman</surname><given-names>JM</given-names></name><name><surname>De Jager</surname><given-names>PL</given-names></name><name><surname>Feany</surname><given-names>MB</given-names></name></person-group><article-title>Parkinson’s disease: genetics and pathogenesis</article-title><source>Annu Rev Pathol</source><year>2011</year><volume>6</volume><fpage>193</fpage><lpage>222</lpage><pub-id pub-id-type="pmid">21034221</pub-id></element-citation></ref><ref id="b211-tacg-5-001"><label>211</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guttmacher</surname><given-names>AE</given-names></name><name><surname>Collins</surname><given-names>FS</given-names></name><name><surname>Carmona</surname><given-names>RH</given-names></name></person-group><article-title>The family history – more important than ever</article-title><source>N Engl J Med</source><year>2004</year><volume>351</volume><issue>22</issue><fpage>2333</fpage><lpage>2336</lpage><pub-id pub-id-type="pmid">15564550</pub-id></element-citation></ref><ref id="b212-tacg-5-001"><label>212</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Papadimitriou</surname><given-names>GN</given-names></name><name><surname>Dikeos</surname><given-names>DG</given-names></name></person-group><article-title>How does recent knowledge on the heredity of schizophrenia affect genetic counseling?</article-title><source>Curr Psychiatry Rep</source><year>2003</year><volume>5</volume><issue>4</issue><fpage>239</fpage><lpage>240</lpage><pub-id pub-id-type="pmid">12857525</pub-id></element-citation></ref><ref id="b213-tacg-5-001"><label>213</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reveley</surname><given-names>A</given-names></name></person-group><article-title>Genetic counselling for schizophrenia</article-title><source>Br J Psychiatry</source><year>1985</year><volume>147</volume><fpage>107</fpage><lpage>112</lpage><pub-id pub-id-type="pmid">4041685</pub-id></element-citation></ref><ref id="b214-tacg-5-001"><label>214</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tsuang</surname><given-names>MT</given-names></name></person-group><article-title>Genetic counseling for psychiatric patients and their families</article-title><source>Am J Psychiatry</source><year>1978</year><volume>135</volume><issue>12</issue><fpage>1465</fpage><lpage>1475</lpage><pub-id pub-id-type="pmid">717559</pub-id></element-citation></ref><ref id="b215-tacg-5-001"><label>215</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hunter</surname><given-names>MJ</given-names></name><name><surname>Hippman</surname><given-names>C</given-names></name><name><surname>Honer</surname><given-names>WG</given-names></name><name><surname>Austin</surname><given-names>JC</given-names></name></person-group><article-title>Genetic counseling for schizophrenia: a review of referrals to a provincial medical genetics program from 1968 to 2007</article-title><source>Am J Med Genet A</source><year>2010</year><volume>152A</volume><issue>1</issue><fpage>147</fpage><lpage>152</lpage><pub-id pub-id-type="pmid">20034078</pub-id></element-citation></ref><ref id="b216-tacg-5-001"><label>216</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lyus</surname><given-names>VL</given-names></name></person-group><article-title>The importance of genetic counseling for individuals with schizophrenia and their relatives: potential clients’ opinions and experiences</article-title><source>Am J Med Genet B Neuropsychiatr Genet</source><year>2007</year><volume>144B</volume><issue>8</issue><fpage>1014</fpage><lpage>1021</lpage><pub-id pub-id-type="pmid">17525978</pub-id></element-citation></ref><ref id="b217-tacg-5-001"><label>217</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Austin</surname><given-names>JC</given-names></name><name><surname>Honer</surname><given-names>WG</given-names></name></person-group><article-title>Psychiatric genetic counselling for parents of individuals affected with psychotic disorders: a pilot study</article-title><source>Early Interv Psychiatry</source><year>2008</year><volume>2</volume><issue>2</issue><fpage>80</fpage><lpage>89</lpage><pub-id pub-id-type="pmid">21352137</pub-id></element-citation></ref><ref id="b218-tacg-5-001"><label>218</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Torrey</surname><given-names>EF</given-names></name></person-group><source>Surviving Schizophrenia: A Manual for Families, Patients, and Providers</source><edition>5th ed</edition><publisher-loc>New York, NY</publisher-loc><publisher-name>Collins</publisher-name><year>2006</year></element-citation></ref><ref id="b219-tacg-5-001"><label>219</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bruder</surname><given-names>CE</given-names></name><name><surname>Piotrowski</surname><given-names>A</given-names></name><name><surname>Gijsbers</surname><given-names>AA</given-names></name><etal></etal></person-group><article-title>Phenotypically concordant and discordant monozygotic twins display different DNA copy-number- variation profiles</article-title><source>Am J Hum Genet</source><year>2008</year><volume>82</volume><issue>3</issue><fpage>763</fpage><lpage>771</lpage><pub-id pub-id-type="pmid">18304490</pub-id></element-citation></ref><ref id="b220-tacg-5-001"><label>220</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dempster</surname><given-names>EL</given-names></name><name><surname>Pidsley</surname><given-names>R</given-names></name><name><surname>Schalkwyk</surname><given-names>LC</given-names></name><etal></etal></person-group><article-title>Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder</article-title><source>Hum Mol Genet</source><year>2011</year><volume>20</volume><issue>24</issue><fpage>4786</fpage><lpage>4796</lpage><pub-id pub-id-type="pmid">21908516</pub-id></element-citation></ref><ref id="b221-tacg-5-001"><label>221</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kato</surname><given-names>T</given-names></name><name><surname>Iwamoto</surname><given-names>K</given-names></name><name><surname>Kakiuchi</surname><given-names>C</given-names></name><name><surname>Kuratomi</surname><given-names>G</given-names></name><name><surname>Okazaki</surname><given-names>Y</given-names></name></person-group><article-title>Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders</article-title><source>Mol Psychiatry</source><year>2005</year><volume>10</volume><issue>7</issue><fpage>622</fpage><lpage>630</lpage><pub-id pub-id-type="pmid">15838537</pub-id></element-citation></ref><ref id="b222-tacg-5-001"><label>222</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maiti</surname><given-names>S</given-names></name><name><surname>Kumar</surname><given-names>KH</given-names></name><name><surname>Castellani</surname><given-names>CA</given-names></name><name><surname>O’Reilly</surname><given-names>R</given-names></name><name><surname>Singh</surname><given-names>SM</given-names></name></person-group><article-title>Ontogenetic de novo copy number variations (CNVs) as a source of genetic individuality: studies on two families with MZD twins for schizophrenia</article-title><source>PLoS One</source><year>2011</year><volume>6</volume><issue>3</issue><fpage>e17125</fpage><pub-id pub-id-type="pmid">21399695</pub-id></element-citation></ref><ref id="b223-tacg-5-001"><label>223</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Husted</surname><given-names>JA</given-names></name><name><surname>Ahmed</surname><given-names>R</given-names></name><name><surname>Chow</surname><given-names>EW</given-names></name><name><surname>Brzustowicz</surname><given-names>LM</given-names></name><name><surname>Bassett</surname><given-names>AS</given-names></name></person-group><article-title>Childhood trauma and genetic factors in familial schizophrenia associated with the NOS1AP gene</article-title><source>Schizophr Res</source><year>2010</year><volume>121</volume><issue>1–3</issue><fpage>187</fpage><lpage>192</lpage><pub-id pub-id-type="pmid">20541371</pub-id></element-citation></ref><ref id="b224-tacg-5-001"><label>224</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Os</surname><given-names>J</given-names></name><name><surname>Kenis</surname><given-names>G</given-names></name><name><surname>Rutten</surname><given-names>BP</given-names></name></person-group><article-title>The environment and schizophrenia</article-title><source>Nature</source><year>2010</year><volume>468</volume><issue>7321</issue><fpage>203</fpage><lpage>212</lpage><pub-id pub-id-type="pmid">21068828</pub-id></element-citation></ref><ref id="b225-tacg-5-001"><label>225</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kurnit</surname><given-names>DM</given-names></name><name><surname>Layton</surname><given-names>WM</given-names></name><name><surname>Matthysse</surname><given-names>S</given-names></name></person-group><article-title>Genetics, chance, and morphogenesis</article-title><source>Am J Hum Genet</source><year>1987</year><volume>41</volume><issue>6</issue><fpage>979</fpage><lpage>995</lpage><pub-id pub-id-type="pmid">3687945</pub-id></element-citation></ref><ref id="b226-tacg-5-001"><label>226</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Ruvinsky</surname><given-names>A</given-names></name></person-group><source>Genetics and Randomness</source><publisher-loc>Boca Raton, FL</publisher-loc><publisher-name>CRC Press</publisher-name><year>2010</year></element-citation></ref><ref id="b227-tacg-5-001"><label>227</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lichtenstein</surname><given-names>P</given-names></name><name><surname>Bjork</surname><given-names>C</given-names></name><name><surname>Hultman</surname><given-names>CM</given-names></name><name><surname>Scolnick</surname><given-names>E</given-names></name><name><surname>Sklar</surname><given-names>P</given-names></name><name><surname>Sullivan</surname><given-names>PF</given-names></name></person-group><article-title>Recurrence risks for schizophrenia in a Swedish national cohort</article-title><source>Psychol Med</source><year>2006</year><volume>36</volume><issue>10</issue><fpage>1417</fpage><lpage>1425</lpage><pub-id pub-id-type="pmid">16863597</pub-id></element-citation></ref><ref id="b228-tacg-5-001"><label>228</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Slatkin</surname><given-names>M</given-names></name></person-group><article-title>Genotype-specific recurrence risks as indicators of the genetic architecture of complex diseases</article-title><source>Am J Hum Genet</source><year>2008</year><volume>83</volume><issue>1</issue><fpage>120</fpage><lpage>126</lpage><pub-id pub-id-type="pmid">18597734</pub-id></element-citation></ref><ref id="b229-tacg-5-001"><label>229</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wray</surname><given-names>NR</given-names></name><name><surname>Goddard</surname><given-names>ME</given-names></name><name><surname>Visscher</surname><given-names>PM</given-names></name></person-group><article-title>Prediction of individual genetic risk to disease from genome-wide association studies</article-title><source>Genome Res</source><year>2007</year><volume>17</volume><issue>10</issue><fpage>1520</fpage><lpage>1528</lpage><pub-id pub-id-type="pmid">17785532</pub-id></element-citation></ref><ref id="b230-tacg-5-001"><label>230</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Slatkin</surname><given-names>M</given-names></name></person-group><article-title>Epigenetic inheritance and the missing heritability problem</article-title><source>Genetics</source><year>2009</year><volume>182</volume><issue>3</issue><fpage>845</fpage><lpage>850</lpage><pub-id pub-id-type="pmid">19416939</pub-id></element-citation></ref><ref id="b231-tacg-5-001"><label>231</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lander</surname><given-names>ES</given-names></name></person-group><article-title>Initial impact of the sequencing of the human genome</article-title><source>Nature</source><year>2011</year><volume>470</volume><issue>7333</issue><fpage>187</fpage><lpage>197</lpage><pub-id pub-id-type="pmid">21307931</pub-id></element-citation></ref><ref id="b232-tacg-5-001"><label>232</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Drmanac</surname><given-names>R</given-names></name></person-group><article-title>The advent of personal genome sequencing</article-title><source>Genet Med</source><year>2011</year><volume>13</volume><issue>3</issue><fpage>188</fpage><lpage>190</lpage><pub-id pub-id-type="pmid">21311341</pub-id></element-citation></ref><ref id="b233-tacg-5-001"><label>233</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greenspan</surname><given-names>SI</given-names></name><name><surname>Brazelton</surname><given-names>TB</given-names></name><name><surname>Cordero</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Guidelines for early identification, screening, and clinical management of children with autism spectrum disorders</article-title><source>Pediatrics</source><year>2008</year><volume>121</volume><issue>4</issue><fpage>828</fpage><lpage>830</lpage><pub-id pub-id-type="pmid">18381546</pub-id></element-citation></ref><ref id="b234-tacg-5-001"><label>234</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miles</surname><given-names>JH</given-names></name></person-group><article-title>Autism spectrum disorders – a genetics review</article-title><source>Genet Med</source><year>2011</year><volume>13</volume><issue>4</issue><fpage>278</fpage><lpage>294</lpage><pub-id pub-id-type="pmid">21358411</pub-id></element-citation></ref><ref id="b235-tacg-5-001"><label>235</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kjeldsen</surname><given-names>MJ</given-names></name><name><surname>Kyvik</surname><given-names>KO</given-names></name><name><surname>Christensen</surname><given-names>K</given-names></name><name><surname>Friis</surname><given-names>ML</given-names></name></person-group><article-title>Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs</article-title><source>Epilepsy Res</source><year>2001</year><volume>44</volume><issue>2–3</issue><fpage>167</fpage><lpage>178</lpage><pub-id pub-id-type="pmid">11325572</pub-id></element-citation></ref><ref id="b236-tacg-5-001"><label>236</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mulley</surname><given-names>JC</given-names></name><name><surname>Dibbens</surname><given-names>LM</given-names></name></person-group><article-title>Genetic variations and associated pathophysiology in the management of epilepsy</article-title><source>The Application of Clinical Genetics</source><year>2011</year><volume>4</volume><fpage>113</fpage><lpage>125</lpage></element-citation></ref><ref id="b237-tacg-5-001"><label>237</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pal</surname><given-names>DK</given-names></name><name><surname>Pong</surname><given-names>AW</given-names></name><name><surname>Chung</surname><given-names>WK</given-names></name></person-group><article-title>Genetic evaluation and counseling for epilepsy</article-title><source>Nat Rev Neurol</source><year>2010</year><volume>6</volume><issue>8</issue><fpage>445</fpage><lpage>453</lpage><pub-id pub-id-type="pmid">20647993</pub-id></element-citation></ref><ref id="b238-tacg-5-001"><label>238</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Poduri</surname><given-names>A</given-names></name><name><surname>Lowenstein</surname><given-names>D</given-names></name></person-group><article-title>Epilepsy genetics – past, present, and future</article-title><source>Curr Opin Genet Dev</source><year>2011</year><volume>21</volume><issue>3</issue><fpage>325</fpage><lpage>332</lpage><pub-id pub-id-type="pmid">21277190</pub-id></element-citation></ref><ref id="b239-tacg-5-001"><label>239</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>K</given-names></name></person-group><article-title>Genetic epidemiology of epilepsy: a twin study</article-title><source>Neurol India</source><year>2005</year><volume>53</volume><issue>1</issue><fpage>93</fpage><lpage>98</lpage><pub-id pub-id-type="pmid">15805664</pub-id></element-citation></ref><ref id="b240-tacg-5-001"><label>240</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Do</surname><given-names>CB</given-names></name><name><surname>Tung</surname><given-names>JY</given-names></name><name><surname>Dorfman</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease</article-title><source>PLoS Genet</source><year>2011</year><volume>7</volume><issue>6</issue><fpage>e1002141</fpage><pub-id pub-id-type="pmid">21738487</pub-id></element-citation></ref><ref id="b241-tacg-5-001"><label>241</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elbaz</surname><given-names>A</given-names></name><name><surname>Bower</surname><given-names>JH</given-names></name><name><surname>Maraganore</surname><given-names>DM</given-names></name><etal></etal></person-group><article-title>Risk tables for parkinsonism and Parkinson’s disease</article-title><source>J Clin Epidemiol</source><year>2002</year><volume>55</volume><issue>1</issue><fpage>25</fpage><lpage>31</lpage><pub-id pub-id-type="pmid">11781119</pub-id></element-citation></ref><ref id="b242-tacg-5-001"><label>242</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schulte</surname><given-names>C</given-names></name><name><surname>Gasser</surname><given-names>T</given-names></name></person-group><article-title>Genetic basis of Parkinson’s disease: inheritance, penetrance, and expression</article-title><source>The Application of Clinical Genetics</source><year>2011</year><volume>4</volume><issue>67–80</issue><fpage>67</fpage></element-citation></ref><ref id="b243-tacg-5-001"><label>243</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toft</surname><given-names>M</given-names></name><name><surname>Ross</surname><given-names>OA</given-names></name></person-group><article-title>Copy number variation in Parkinson’s disease</article-title><source>Genome Med</source><year>2010</year><volume>2</volume><issue>9</issue><fpage>62</fpage><pub-id pub-id-type="pmid">20828427</pub-id></element-citation></ref><ref id="b244-tacg-5-001"><label>244</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ballard</surname><given-names>C</given-names></name><name><surname>Gauthier</surname><given-names>S</given-names></name><name><surname>Corbett</surname><given-names>A</given-names></name><name><surname>Brayne</surname><given-names>C</given-names></name><name><surname>Aarsland</surname><given-names>D</given-names></name><name><surname>Jones</surname><given-names>E</given-names></name></person-group><article-title>Alzheimer’s disease</article-title><source>Lancet</source><year>2011</year><volume>377</volume><issue>9770</issue><fpage>1019</fpage><lpage>1031</lpage><pub-id pub-id-type="pmid">21371747</pub-id></element-citation></ref><ref id="b245-tacg-5-001"><label>245</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bertram</surname><given-names>L</given-names></name><name><surname>Lill</surname><given-names>CM</given-names></name><name><surname>Tanzi</surname><given-names>RE</given-names></name></person-group><article-title>The genetics of Alzheimer disease: back to the future</article-title><source>Neuron</source><year>2010</year><volume>68</volume><issue>2</issue><fpage>270</fpage><lpage>281</lpage><pub-id pub-id-type="pmid">20955934</pub-id></element-citation></ref><ref id="b246-tacg-5-001"><label>246</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gatz</surname><given-names>M</given-names></name><name><surname>Reynolds</surname><given-names>CA</given-names></name><name><surname>Fratiglioni</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Role of genes and environments for explaining Alzheimer disease</article-title><source>Arch Gen Psychiatry</source><year>2006</year><volume>63</volume><issue>2</issue><fpage>168</fpage><lpage>174</lpage><pub-id pub-id-type="pmid">16461860</pub-id></element-citation></ref><ref id="b247-tacg-5-001"><label>247</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goldman</surname><given-names>JS</given-names></name><name><surname>Hahn</surname><given-names>SE</given-names></name><name><surname>Catania</surname><given-names>JW</given-names></name><etal></etal></person-group><article-title>Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors</article-title><source>Genet Med</source><year>2011</year><volume>13</volume><issue>6</issue><fpage>597</fpage><lpage>605</lpage><pub-id pub-id-type="pmid">21577118</pub-id></element-citation></ref><ref id="b248-tacg-5-001"><label>248</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Coulter</surname><given-names>ME</given-names></name><name><surname>Miller</surname><given-names>DT</given-names></name><name><surname>Harris</surname><given-names>DJ</given-names></name><etal></etal></person-group><article-title>Chromosomal microarray testing influences medical management</article-title><source>Genet Med</source><year>2011</year><volume>13</volume><issue>9</issue><fpage>770</fpage><lpage>776</lpage><pub-id pub-id-type="pmid">21716121</pub-id></element-citation></ref><ref id="b249-tacg-5-001"><label>249</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Basel-Vanagaite</surname><given-names>L</given-names></name><name><surname>Goldberg-Stern</surname><given-names>H</given-names></name><name><surname>Mimouni-Bloch</surname><given-names>A</given-names></name><name><surname>Shkalim</surname><given-names>V</given-names></name><name><surname>Bohm</surname><given-names>D</given-names></name><name><surname>Kohlhase</surname><given-names>J</given-names></name></person-group><article-title>An emerging 1q21.1 deletion-associated neurodevelopmental phenotype</article-title><source>J Child Neurol</source><year>2011</year><volume>26</volume><issue>1</issue><fpage>113</fpage><lpage>116</lpage><pub-id pub-id-type="pmid">21212457</pub-id></element-citation></ref><ref id="b250-tacg-5-001"><label>250</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brunet</surname><given-names>A</given-names></name><name><surname>Armengol</surname><given-names>L</given-names></name><name><surname>Heine</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1</article-title><source>BMC Med Genet</source><year>2009</year><volume>10</volume><fpage>144</fpage><pub-id pub-id-type="pmid">20030804</pub-id></element-citation></ref><ref id="b251-tacg-5-001"><label>251</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christiansen</surname><given-names>J</given-names></name><name><surname>Dyck</surname><given-names>JD</given-names></name><name><surname>Elyas</surname><given-names>BG</given-names></name><etal></etal></person-group><article-title>Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease</article-title><source>Circ Res</source><year>2004</year><volume>94</volume><issue>11</issue><fpage>1429</fpage><lpage>1435</lpage><pub-id pub-id-type="pmid">15117819</pub-id></element-citation></ref><ref id="b252-tacg-5-001"><label>252</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ikeda</surname><given-names>M</given-names></name><name><surname>Aleksic</surname><given-names>B</given-names></name><name><surname>Kirov</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Copy number variation in schizophrenia in the Japanese population</article-title><source>Biol Psychiatry</source><year>2010</year><volume>67</volume><issue>3</issue><fpage>283</fpage><lpage>286</lpage><pub-id pub-id-type="pmid">19880096</pub-id></element-citation></ref><ref id="b253-tacg-5-001"><label>253</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sahoo</surname><given-names>T</given-names></name><name><surname>Theisen</surname><given-names>A</given-names></name><name><surname>Rosenfeld</surname><given-names>JA</given-names></name><etal></etal></person-group><article-title>Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems</article-title><source>Genet Med</source><year>2011</year><volume>13</volume><issue>10</issue><fpage>868</fpage><lpage>880</lpage><pub-id pub-id-type="pmid">21792059</pub-id></element-citation></ref><ref id="b254-tacg-5-001"><label>254</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vu</surname><given-names>TH</given-names></name><name><surname>Coccaro</surname><given-names>EF</given-names></name><name><surname>Eichler</surname><given-names>EE</given-names></name><name><surname>Girirajan</surname><given-names>S</given-names></name></person-group><article-title>Genomic architecture of aggression: rare copy number variants in intermittent explosive disorder</article-title><source>Am J Med Genet B Neuropsychiatr Genet</source><year>2011</year><volume>156B</volume><issue>7</issue><fpage>808</fpage><lpage>816</lpage><pub-id pub-id-type="pmid">21812102</pub-id></element-citation></ref><ref id="b255-tacg-5-001"><label>255</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ballif</surname><given-names>BC</given-names></name><name><surname>Theisen</surname><given-names>A</given-names></name><name><surname>Coppinger</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication</article-title><source>Mol Cytogenet</source><year>2008</year><volume>1</volume><fpage>8</fpage><pub-id pub-id-type="pmid">18471269</pub-id></element-citation></ref><ref id="b256-tacg-5-001"><label>256</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clayton-Smith</surname><given-names>J</given-names></name><name><surname>Giblin</surname><given-names>C</given-names></name><name><surname>Smith</surname><given-names>RA</given-names></name><name><surname>Dunn</surname><given-names>C</given-names></name><name><surname>Willatt</surname><given-names>L</given-names></name></person-group><article-title>Familial 3q29 microdeletion syndrome providing further evidence of involvement of the 3q29 region in bipolar disorder</article-title><source>Clin Dysmorphol</source><year>2010</year><volume>19</volume><issue>3</issue><fpage>128</fpage><lpage>132</lpage><pub-id pub-id-type="pmid">20453639</pub-id></element-citation></ref><ref id="b257-tacg-5-001"><label>257</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Digilio</surname><given-names>MC</given-names></name><name><surname>Bernardini</surname><given-names>L</given-names></name><name><surname>Mingarelli</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>3q29 Microdeletion: a mental retardation disorder unassociated with a recognizable phenotype in two mother–daughter pairs</article-title><source>Am J Med Genet A</source><year>2009</year><volume>149A</volume><issue>8</issue><fpage>1777</fpage><lpage>1781</lpage><pub-id pub-id-type="pmid">19610115</pub-id></element-citation></ref><ref id="b258-tacg-5-001"><label>258</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mulle</surname><given-names>JG</given-names></name><name><surname>Dodd</surname><given-names>AF</given-names></name><name><surname>McGrath</surname><given-names>JA</given-names></name><etal></etal></person-group><article-title>Microdeletions of 3q29 confer high risk for schizophrenia</article-title><source>Am J Hum Genet</source><year>2010</year><volume>87</volume><issue>2</issue><fpage>229</fpage><lpage>236</lpage><pub-id pub-id-type="pmid">20691406</pub-id></element-citation></ref><ref id="b259-tacg-5-001"><label>259</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Quintero-Rivera</surname><given-names>F</given-names></name><name><surname>Sharifi-Hannauer</surname><given-names>P</given-names></name><name><surname>Martinez-Agosto</surname><given-names>JA</given-names></name></person-group><article-title>Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review</article-title><source>Am J Med Genet A</source><year>2010</year><volume>152A</volume><issue>10</issue><fpage>2459</fpage><lpage>2467</lpage><pub-id pub-id-type="pmid">20830797</pub-id></element-citation></ref><ref id="b260-tacg-5-001"><label>260</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vacic</surname><given-names>V</given-names></name><name><surname>McCarthy</surname><given-names>S</given-names></name><name><surname>Malhotra</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia</article-title><source>Nature</source><year>2011</year><volume>471</volume><issue>7339</issue><fpage>499</fpage><lpage>503</lpage><pub-id pub-id-type="pmid">21346763</pub-id></element-citation></ref><ref id="b261-tacg-5-001"><label>261</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Willatt</surname><given-names>L</given-names></name><name><surname>Cox</surname><given-names>J</given-names></name><name><surname>Barber</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome</article-title><source>Am J Hum Genet</source><year>2005</year><volume>77</volume><issue>1</issue><fpage>154</fpage><lpage>160</lpage><pub-id pub-id-type="pmid">15918153</pub-id></element-citation></ref><ref id="b262-tacg-5-001"><label>262</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Browne</surname><given-names>CE</given-names></name><name><surname>Dennis</surname><given-names>NR</given-names></name><name><surname>Maher</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>Inherited interstitial duplications of proximal 15q: genotype-phenotype correlations</article-title><source>Am J Hum Genet</source><year>1997</year><volume>61</volume><issue>6</issue><fpage>1342</fpage><lpage>1352</lpage><pub-id pub-id-type="pmid">9399882</pub-id></element-citation></ref><ref id="b263-tacg-5-001"><label>263</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chamberlain</surname><given-names>SJ</given-names></name><name><surname>Lalande</surname><given-names>M</given-names></name></person-group><article-title>Neurodevelopmental disorders involving genomic imprinting at human chromosome 15q11-q13</article-title><source>Neurobiol Dis</source><year>2010</year><volume>39</volume><issue>1</issue><fpage>13</fpage><lpage>20</lpage><pub-id pub-id-type="pmid">20304067</pub-id></element-citation></ref><ref id="b264-tacg-5-001"><label>264</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cook</surname><given-names>EH</given-names><suffix>Jr</suffix></name><name><surname>Lindgren</surname><given-names>V</given-names></name><name><surname>Leventhal</surname><given-names>BL</given-names></name><etal></etal></person-group><article-title>Autism or atypical autism in maternally but not paternally derived proximal 15q duplication</article-title><source>Am J Hum Genet</source><year>1997</year><volume>60</volume><issue>4</issue><fpage>928</fpage><lpage>934</lpage><pub-id pub-id-type="pmid">9106540</pub-id></element-citation></ref><ref id="b265-tacg-5-001"><label>265</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gurrieri</surname><given-names>F</given-names></name><name><surname>Battaglia</surname><given-names>A</given-names></name><name><surname>Torrisi</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Pervasive developmental disorder and epilepsy due to maternally derived duplication of 15q11-q13</article-title><source>Neurology</source><year>1999</year><volume>52</volume><issue>8</issue><fpage>1694</fpage><lpage>1697</lpage><pub-id pub-id-type="pmid">10331703</pub-id></element-citation></ref><ref id="b266-tacg-5-001"><label>266</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hogart</surname><given-names>A</given-names></name><name><surname>Wu</surname><given-names>D</given-names></name><name><surname>LaSalle</surname><given-names>JM</given-names></name><name><surname>Schanen</surname><given-names>NC</given-names></name></person-group><article-title>The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13</article-title><source>Neurobiol Dis</source><year>2010</year><volume>38</volume><issue>2</issue><fpage>181</fpage><lpage>191</lpage><pub-id pub-id-type="pmid">18840528</pub-id></element-citation></ref><ref id="b267-tacg-5-001"><label>267</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Michelson</surname><given-names>M</given-names></name><name><surname>Eden</surname><given-names>A</given-names></name><name><surname>Vinkler</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Familial partial trisomy 15q11-13 presenting as intractable epilepsy in the child and schizophrenia in the mother</article-title><source>Eur J Paediatr Neurol</source><year>2011</year><volume>15</volume><issue>3</issue><fpage>230</fpage><lpage>233</lpage><pub-id pub-id-type="pmid">21145272</pub-id></element-citation></ref><ref id="b268-tacg-5-001"><label>268</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thomas</surname><given-names>JA</given-names></name><name><surname>Johnson</surname><given-names>J</given-names></name><name><surname>Peterson Kraai</surname><given-names>TL</given-names></name><etal></etal></person-group><article-title>Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment</article-title><source>Am J Med Genet A</source><year>2003</year><volume>119A</volume><issue>2</issue><fpage>111</fpage><lpage>120</lpage><pub-id pub-id-type="pmid">12749048</pub-id></element-citation></ref><ref id="b269-tacg-5-001"><label>269</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ben-Shachar</surname><given-names>S</given-names></name><name><surname>Lanpher</surname><given-names>B</given-names></name><name><surname>German</surname><given-names>JR</given-names></name><etal></etal></person-group><article-title>Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders</article-title><source>J Med Genet</source><year>2009</year><volume>46</volume><issue>6</issue><fpage>382</fpage><lpage>388</lpage><pub-id pub-id-type="pmid">19289393</pub-id></element-citation></ref><ref id="b270-tacg-5-001"><label>270</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Bon</surname><given-names>BW</given-names></name><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Menten</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome</article-title><source>J Med Genet</source><year>2009</year><volume>46</volume><issue>8</issue><fpage>511</fpage><lpage>523</lpage><pub-id pub-id-type="pmid">19372089</pub-id></element-citation></ref><ref id="b271-tacg-5-001"><label>271</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cubells</surname><given-names>JF</given-names></name><name><surname>Deoreo</surname><given-names>EH</given-names></name><name><surname>Harvey</surname><given-names>PD</given-names></name><etal></etal></person-group><article-title>Pharmaco-genetically guided treatment of recurrent rage outbursts in an adult male with 15q13.3 deletion syndrome</article-title><source>Am J Med Genet A</source><year>2011</year><volume>155A</volume><issue>4</issue><fpage>805</fpage><lpage>810</lpage><pub-id pub-id-type="pmid">21594999</pub-id></element-citation></ref><ref id="b272-tacg-5-001"><label>272</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dibbens</surname><given-names>LM</given-names></name><name><surname>Mullen</surname><given-names>S</given-names></name><name><surname>Helbig</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance</article-title><source>Hum Mol Genet</source><year>2009</year><volume>18</volume><issue>19</issue><fpage>3626</fpage><lpage>3631</lpage><pub-id pub-id-type="pmid">19592580</pub-id></element-citation></ref><ref id="b273-tacg-5-001"><label>273</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Helbig</surname><given-names>I</given-names></name><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Sharp</surname><given-names>AJ</given-names></name><etal></etal></person-group><article-title>15q13.3 microdeletions increase risk of idiopathic generalized epilepsy</article-title><source>Nat Genet</source><year>2009</year><volume>41</volume><issue>2</issue><fpage>160</fpage><lpage>162</lpage><pub-id pub-id-type="pmid">19136953</pub-id></element-citation></ref><ref id="b274-tacg-5-001"><label>274</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Masurel-Paulet</surname><given-names>A</given-names></name><name><surname>Andrieux</surname><given-names>J</given-names></name><name><surname>Callier</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Delineation of 15q13.3 microdeletions</article-title><source>Clin Genet</source><year>2010</year><volume>78</volume><issue>2</issue><fpage>149</fpage><lpage>161</lpage><pub-id pub-id-type="pmid">20236110</pub-id></element-citation></ref><ref id="b275-tacg-5-001"><label>275</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>DT</given-names></name><name><surname>Shen</surname><given-names>Y</given-names></name><name><surname>Weiss</surname><given-names>LA</given-names></name><etal></etal></person-group><article-title>Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders</article-title><source>J Med Genet</source><year>2009</year><volume>46</volume><issue>4</issue><fpage>242</fpage><lpage>248</lpage><pub-id pub-id-type="pmid">18805830</pub-id></element-citation></ref><ref id="b276-tacg-5-001"><label>276</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pagnamenta</surname><given-names>AT</given-names></name><name><surname>Wing</surname><given-names>K</given-names></name><name><surname>Sadighi Akha</surname><given-names>E</given-names></name><etal></etal></person-group><article-title>A 15q13.3 microdeletion segregating with autism</article-title><source>Eur J Hum Genet</source><year>2009</year><volume>17</volume><issue>5</issue><fpage>687</fpage><lpage>692</lpage><pub-id pub-id-type="pmid">19050728</pub-id></element-citation></ref><ref id="b277-tacg-5-001"><label>277</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sharp</surname><given-names>AJ</given-names></name><name><surname>Mefford</surname><given-names>HC</given-names></name><name><surname>Li</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures</article-title><source>Nat Genet</source><year>2008</year><volume>40</volume><issue>3</issue><fpage>322</fpage><lpage>328</lpage><pub-id pub-id-type="pmid">18278044</pub-id></element-citation></ref><ref id="b278-tacg-5-001"><label>278</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shinawi</surname><given-names>M</given-names></name><name><surname>Schaaf</surname><given-names>CP</given-names></name><name><surname>Bhatt</surname><given-names>SS</given-names></name><etal></etal></person-group><article-title>A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes</article-title><source>Nat Genet</source><year>2009</year><volume>41</volume><issue>12</issue><fpage>1269</fpage><lpage>1271</lpage><pub-id pub-id-type="pmid">19898479</pub-id></element-citation></ref><ref id="b279-tacg-5-001"><label>279</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bedoyan</surname><given-names>JK</given-names></name><name><surname>Kumar</surname><given-names>RA</given-names></name><name><surname>Sudi</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Duplication 16p11.2 in a child with infantile seizure disorder</article-title><source>Am J Med Genet A</source><year>2010</year><volume>152A</volume><issue>6</issue><fpage>1567</fpage><lpage>1574</lpage><pub-id pub-id-type="pmid">20503337</pub-id></element-citation></ref><ref id="b280-tacg-5-001"><label>280</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fernandez</surname><given-names>BA</given-names></name><name><surname>Roberts</surname><given-names>W</given-names></name><name><surname>Chung</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder</article-title><source>J Med Genet</source><year>2010</year><volume>47</volume><issue>3</issue><fpage>195</fpage><lpage>203</lpage><pub-id pub-id-type="pmid">19755429</pub-id></element-citation></ref><ref id="b281-tacg-5-001"><label>281</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lionel</surname><given-names>AC</given-names></name><name><surname>Crosbie</surname><given-names>J</given-names></name><name><surname>Barbosa</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD</article-title><source>Sci Transl Med</source><year>2011</year><volume>3</volume><issue>95</issue><fpage>95ra75</fpage></element-citation></ref><ref id="b282-tacg-5-001"><label>282</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McCarthy</surname><given-names>SE</given-names></name><name><surname>Makarov</surname><given-names>V</given-names></name><name><surname>Kirov</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Microduplications of 16p11.2 are associated with schizophrenia</article-title><source>Nat Genet</source><year>2009</year><volume>41</volume><issue>11</issue><fpage>1223</fpage><lpage>1227</lpage><pub-id pub-id-type="pmid">19855392</pub-id></element-citation></ref><ref id="b283-tacg-5-001"><label>283</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marshall</surname><given-names>CR</given-names></name><name><surname>Noor</surname><given-names>A</given-names></name><name><surname>Vincent</surname><given-names>JB</given-names></name><etal></etal></person-group><article-title>Structural variation of chromosomes in autism spectrum disorder</article-title><source>Am J Hum Genet</source><year>2008</year><volume>82</volume><issue>2</issue><fpage>477</fpage><lpage>488</lpage><pub-id pub-id-type="pmid">18252227</pub-id></element-citation></ref><ref id="b284-tacg-5-001"><label>284</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rosenfeld</surname><given-names>JA</given-names></name><name><surname>Coppinger</surname><given-names>J</given-names></name><name><surname>Bejjani</surname><given-names>BA</given-names></name><etal></etal></person-group><article-title>Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications</article-title><source>J Neurodev Disord</source><year>2010</year><volume>2</volume><issue>1</issue><fpage>26</fpage><lpage>38</lpage><pub-id pub-id-type="pmid">21731881</pub-id></element-citation></ref><ref id="b285-tacg-5-001"><label>285</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schaaf</surname><given-names>CP</given-names></name><name><surname>Goin-Kochel</surname><given-names>RP</given-names></name><name><surname>Nowell</surname><given-names>KP</given-names></name><etal></etal></person-group><article-title>Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: three patients with syringomyelia</article-title><source>Eur J Hum Genet</source><year>2011</year><volume>19</volume><issue>2</issue><fpage>152</fpage><lpage>156</lpage><pub-id pub-id-type="pmid">20959866</pub-id></element-citation></ref><ref id="b286-tacg-5-001"><label>286</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shen</surname><given-names>Y</given-names></name><name><surname>Dies</surname><given-names>KA</given-names></name><name><surname>Holm</surname><given-names>IA</given-names></name><etal></etal></person-group><article-title>Clinical genetic testing for patients with autism spectrum disorders</article-title><source>Pediatrics</source><year>2010</year><volume>125</volume><issue>4</issue><fpage>e727</fpage><lpage>e735</lpage><pub-id pub-id-type="pmid">20231187</pub-id></element-citation></ref><ref id="b287-tacg-5-001"><label>287</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shinawi</surname><given-names>M</given-names></name><name><surname>Liu</surname><given-names>P</given-names></name><name><surname>Kang</surname><given-names>SH</given-names></name><etal></etal></person-group><article-title>Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size</article-title><source>J Med Genet</source><year>2010</year><volume>47</volume><issue>5</issue><fpage>332</fpage><lpage>341</lpage><pub-id pub-id-type="pmid">19914906</pub-id></element-citation></ref><ref id="b288-tacg-5-001"><label>288</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weiss</surname><given-names>LA</given-names></name><name><surname>Shen</surname><given-names>Y</given-names></name><name><surname>Korn</surname><given-names>JM</given-names></name><etal></etal></person-group><article-title>Association between microdeletion and microduplication at 16p11.2 and autism</article-title><source>N Engl J Med</source><year>2008</year><volume>358</volume><issue>7</issue><fpage>667</fpage><lpage>675</lpage><pub-id pub-id-type="pmid">18184952</pub-id></element-citation></ref><ref id="b289-tacg-5-001"><label>289</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goodship</surname><given-names>J</given-names></name><name><surname>Cross</surname><given-names>I</given-names></name><name><surname>LiLing</surname><given-names>J</given-names></name><name><surname>Wren</surname><given-names>C</given-names></name></person-group><article-title>A population study of chromosome 22q11 deletions in infancy</article-title><source>Arch Dis Child</source><year>1998</year><volume>79</volume><issue>4</issue><fpage>348</fpage><lpage>351</lpage><pub-id pub-id-type="pmid">9875047</pub-id></element-citation></ref><ref id="b290-tacg-5-001"><label>290</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rees</surname><given-names>E</given-names></name><name><surname>Moskvina</surname><given-names>V</given-names></name><name><surname>Owen</surname><given-names>MJ</given-names></name><name><surname>O’Donovan</surname><given-names>MC</given-names></name><name><surname>Kirov</surname><given-names>G</given-names></name></person-group><article-title>De novo rates and selection of schizophrenia-associated copy number variants</article-title><source>Biol Psychiatry</source><year>2011</year><volume>70</volume><issue>12</issue><fpage>1109</fpage><lpage>1114</lpage><pub-id pub-id-type="pmid">21855053</pub-id></element-citation></ref><ref id="b291-tacg-5-001"><label>291</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vassos</surname><given-names>E</given-names></name><name><surname>Collier</surname><given-names>DA</given-names></name><name><surname>Holden</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Penetrance for copy number variants associated with schizophrenia</article-title><source>Hum Mol Genet</source><year>2010</year><volume>19</volume><issue>17</issue><fpage>3477</fpage><lpage>3481</lpage><pub-id pub-id-type="pmid">20587603</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="f1-tacg-5-001" position="float"><label>Figure 1</label><caption><p>Neurodevelopmental model of schizophrenia, informed by new molecular genetic discoveries. One or more transmitted or de novo sequence or structural mutations, involving one or more genes, and acting individually or interactively, is proposed as the initial causal event. The pathway from genotype to phenotype is formulated as a dynamic process beginning at or before conception, and involving gene expression (including, but not limited to, protein activity) and interaction with normal brain development and neuronal plasticity mechanisms, and likely multiple other genetic and non-genetic factors. Different phenotypic endpoints are possible, and specific factors that dictate variable expression of ostensibly the same genetic loading are largely unknown and may be variant-specific. These resulting phenotypes could include clinically diagnosable schizophrenia, other psychiatric illnesses, other conditions including disorders of development, or no detectable expression. For example, a 22q11.2 deletion (yellow structural variant) may be expressed as schizophrenia and/or a related psychiatric disorder and/or another developmental disorder (yellow stars). </p><p><bold>Note:</bold> Adapted from AS Bassett, EW Chow, S O’Neill, LM Brzustowicz, Genetic insights into the neurodevelopmental hypothesis of schizophrenia, <italic>Schizophrenia Bulletin</italic>, 2001, 27, 3, pp. 417–430, by permission of Oxford University Press.<xref ref-type="bibr" rid="b35-tacg-5-001">35</xref></p><p><bold>Abbreviation:</bold> CNV, copy number variation.</p></caption><graphic xlink:href="tacg-5-001f1"></graphic></fig><table-wrap id="t1-tacg-5-001" position="float"><label>Table 1</label><caption><p>Schizophrenia within the context of other common complex neuropsychiatric diseases (as of 2011)</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1">Schizophrenia</th><th align="left" valign="top" rowspan="1" colspan="1">ASD</th><th align="left" valign="top" rowspan="1" colspan="1">Epilepsy</th><th align="left" valign="top" rowspan="1" colspan="1">Parkinson disease</th><th align="left" valign="top" rowspan="1" colspan="1">Alzheimer disease</th></tr></thead><tbody><tr><td colspan="6" align="left" valign="top" rowspan="1"><bold>Clinical features</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Approximate lifetime risk</td><td align="left" valign="top" rowspan="1" colspan="1">~1%</td><td align="left" valign="top" rowspan="1" colspan="1">~1%</td><td align="left" valign="top" rowspan="1" colspan="1">~0.5%</td><td align="left" valign="top" rowspan="1" colspan="1">~1.6%<xref ref-type="table-fn" rid="tfn2-tacg-5-001">a</xref></td><td align="left" valign="top" rowspan="1" colspan="1">~10%<xref ref-type="table-fn" rid="tfn2-tacg-5-001">a</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Typical onset</td><td align="left" valign="top" rowspan="1" colspan="1">Young adulthood</td><td align="left" valign="top" rowspan="1" colspan="1">Early childhood</td><td align="left" valign="top" rowspan="1" colspan="1">Childhood</td><td align="left" valign="top" rowspan="1" colspan="1">Mid to late adulthood</td><td align="left" valign="top" rowspan="1" colspan="1">Mid to late adulthood</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Clinical heterogeneity</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Clinical diagnostic imaging/biomarker(s)/test(s)</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Definitive neuropathological diagnosis</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Primary mode of neuropathogenesis</td><td align="left" valign="top" rowspan="1" colspan="1">Developmental</td><td align="left" valign="top" rowspan="1" colspan="1">Developmental</td><td align="left" valign="top" rowspan="1" colspan="1">Developmental</td><td align="left" valign="top" rowspan="1" colspan="1">Degenerative</td><td align="left" valign="top" rowspan="1" colspan="1">Degenerative</td></tr><tr><td colspan="6" align="left" valign="top" rowspan="1"><bold>Genetic features</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Heritability</td><td align="left" valign="top" rowspan="1" colspan="1">>80%</td><td align="left" valign="top" rowspan="1" colspan="1">~90%</td><td align="left" valign="top" rowspan="1" colspan="1">~45%<xref ref-type="table-fn" rid="tfn3-tacg-5-001">b</xref></td><td align="left" valign="top" rowspan="1" colspan="1">~30%</td><td align="left" valign="top" rowspan="1" colspan="1">~70%</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Genetic heterogeneity</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Major common variant(s)</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Rare sequence mutation subtype(s)</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Rare chromosomal anomaly/structural mutation subtype(s)</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Genetic diagnosis changes medical management<xref ref-type="table-fn" rid="tfn4-tacg-5-001">c</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Pharmacogenetics as standard of care</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Routine use of genome-wide scans<xref ref-type="table-fn" rid="tfn5-tacg-5-001">d</xref></td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td><td align="left" valign="top" rowspan="1" colspan="1">No</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Family history as predominant recurrence risk factor</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Sources (reference numbers)</td><td align="left" valign="top" rowspan="1" colspan="1">See text<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b61-tacg-5-001">61</xref>, <xref ref-type="bibr" rid="b190-tacg-5-001">190</xref>, <xref ref-type="bibr" rid="b233-tacg-5-001">233</xref>, <xref ref-type="bibr" rid="b234-tacg-5-001">234</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b235-tacg-5-001">235</xref>–<xref ref-type="bibr" rid="b239-tacg-5-001">239</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b240-tacg-5-001">240</xref>–<xref ref-type="bibr" rid="b243-tacg-5-001">243</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b244-tacg-5-001">244</xref>–<xref ref-type="bibr" rid="b247-tacg-5-001">247</xref></td></tr></tbody></table><table-wrap-foot><fn id="tfn1-tacg-5-001"><p><bold>Notes:</bold></p></fn><fn id="tfn2-tacg-5-001"><label>a</label><p>Estimated based on risk after age 55–65 years, and therefore highly dependent on the mean life expectancy of the population;</p></fn><fn id="tfn3-tacg-5-001"><label>b</label><p>no consensus estimate, with a wide range of reports in the literature;<xref ref-type="bibr" rid="b235-tacg-5-001">235</xref>,<xref ref-type="bibr" rid="b239-tacg-5-001">239</xref></p></fn><fn id="tfn4-tacg-5-001"><label>c</label><p>management changed for the associated neuropsychiatric disease; this does not include more informed genetic counseling, the precipitation of other referrals or investigations,<xref ref-type="bibr" rid="b248-tacg-5-001">248</xref> or the potential for earlier/more aggressive treatment as a result of early clinical diagnosis because of an increased index of suspicion;</p></fn><fn id="tfn5-tacg-5-001"><label>d</label><p>without accompanying developmental delay/mental retardation, ASD, or multiple congenital anomalies.</p></fn><fn id="tfn6-tacg-5-001"><p><bold>Abbreviation:</bold> ASD, autism spectrum disorder.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t2-tacg-5-001" position="float"><label>Table 2</label><caption><p>Potential future roles for molecular genetics in the clinical management of schizophrenia</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1">Area of benefit</th><th align="left" valign="top" rowspan="1" colspan="1">Details and examples</th></tr></thead><tbody><tr><td colspan="2" align="left" valign="top" rowspan="1"><bold>Medical</bold> (of primary benefit to the clinician and patient)</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Prediction and prevention</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Personalized genetic (ie, inborn) lifetime risk for psychosis<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Narrowing of window for age at onset in high risk cases</p></list-item><list-item><p>Personalized neurocognitive and/or neuroimaging precursors of psychosis</p></list-item><list-item><p>Opportunity to limit important deleterious gene by environment interactions</p></list-item><list-item><p>Anticipation of potential extra-psychiatric features<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Tailored early interventions to delay or prevent onset, or attenuate course</p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Diagnosis</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>At first onset of psychosis, higher index of suspicion for schizophrenia (as a result of improvements in prediction)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Management</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Coordinated multisystem management and anticipatory care for possible extra-psychiatric manifestations of causal genetic variant(s)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Treatment</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Earlier/more aggressive treatment (as a result of improvements in prediction and diagnosis)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Preference for or avoidance of particular antipsychotic medications</p></list-item><list-item><p>Tailored dosing (eg, via knowledge of fast and slow metabolizers; pharmacogenomics)</p></list-item><list-item><p>Less potential confusion of medication side effects with extra-psychiatric manifestations of causal genetic variant(s) (eg, metabolic syndrome, parkinsonism, seizures)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Novel personalized therapeutic targets</p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Prognosis</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Improved course (as a result of improvements in prediction/prevention, diagnosis, treatment, and management)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Personalized data on natural history and longevity<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr><tr><td colspan="2" align="left" valign="top" rowspan="1"><bold>Psychosocial</bold> (of primary benefit to the patient and family)</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Understanding</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Partial answer to the question, “Why me?”<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Explanation for potential premorbid developmental signs and symptoms (eg, learning difficulties)<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Extra reassurance that parenting or personal life choices did not play a major role in causing the illness<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Counseling</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Personalized recurrence risks for family members<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Better informed reproductive decision making and possibility for prenatal detection<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Hope</td><td align="left" valign="top" rowspan="1" colspan="1"><list list-type="bullet"><list-item><p>Proof of progress in understanding the illness<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item><list-item><p>Prospect of continued improvements in treatment and management, as above<xref ref-type="table-fn" rid="tfn8-tacg-5-001">*</xref></p></list-item></list></td></tr></tbody></table><table-wrap-foot><fn id="tfn7-tacg-5-001"><p><bold>Note:</bold></p></fn><fn id="tfn8-tacg-5-001"><label>*</label><p>Already possible for 22q11.2 deletion syndrome (22q11.2DS) subtype of schizophrenia (see text for details).</p></fn></table-wrap-foot></table-wrap><table-wrap id="t3-tacg-5-001" position="float"><label>Table 3</label><caption><p>The current established and emerging genetic subtypes of schizophrenia are characterized by large, rare, recurring copy number variation and variable expressivity</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="3" colspan="1">Genetic subtype of schizophrenia</th><th align="left" valign="top" rowspan="1" colspan="1">Established</th><th colspan="5" align="left" valign="top" rowspan="1">Emerging</th></tr><tr><th align="left" valign="top" rowspan="1" colspan="1"><hr></hr></th><th colspan="5" align="left" valign="top" rowspan="1"><hr></hr></th></tr><tr><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"></th></tr></thead><tbody><tr><td colspan="7" align="left" valign="top" rowspan="1"><bold>Genotype</bold></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Locus</td><td align="left" valign="top" rowspan="1" colspan="1">22q11.2</td><td align="left" valign="top" rowspan="1" colspan="1">1q21.1</td><td align="left" valign="top" rowspan="1" colspan="1">3q29</td><td align="left" valign="top" rowspan="1" colspan="1">15q11-q13</td><td align="left" valign="top" rowspan="1" colspan="1">15q13.3</td><td align="left" valign="top" rowspan="1" colspan="1">16p11.2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Copy number change</td><td align="left" valign="top" rowspan="1" colspan="1">Loss</td><td align="left" valign="top" rowspan="1" colspan="1">Loss</td><td align="left" valign="top" rowspan="1" colspan="1">Loss</td><td align="left" valign="top" rowspan="1" colspan="1">Gain<xref ref-type="table-fn" rid="tfn10-tacg-5-001">a</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Loss</td><td align="left" valign="top" rowspan="1" colspan="1">Gain</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Typical size</td><td align="left" valign="top" rowspan="1" colspan="1">3.0 Mb</td><td align="left" valign="top" rowspan="1" colspan="1">1.4 Mb</td><td align="left" valign="top" rowspan="1" colspan="1">1.6 Mb</td><td align="left" valign="top" rowspan="1" colspan="1">6.0 Mb</td><td align="left" valign="top" rowspan="1" colspan="1">1.5 Mb</td><td align="left" valign="top" rowspan="1" colspan="1">0.6 Mb</td></tr><tr><td colspan="7" align="left" valign="top" rowspan="1"><bold>Phenotype</bold><xref ref-type="table-fn" rid="tfn11-tacg-5-001">b</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MIM number</td><td align="left" valign="top" rowspan="1" colspan="1">188400/192430</td><td align="left" valign="top" rowspan="1" colspan="1">612474</td><td align="left" valign="top" rowspan="1" colspan="1">609425</td><td align="left" valign="top" rowspan="1" colspan="1">608636</td><td align="left" valign="top" rowspan="1" colspan="1">612001</td><td align="left" valign="top" rowspan="1" colspan="1">611913</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Schizophrenia</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Other psychiatric illnesses<xref ref-type="table-fn" rid="tfn12-tacg-5-001">c</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes<xref ref-type="table-fn" rid="tfn13-tacg-5-001">d</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes<xref ref-type="table-fn" rid="tfn13-tacg-5-001">d</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ASDs</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes<xref ref-type="table-fn" rid="tfn13-tacg-5-001">d</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Developmental delay/mental retardation</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Seizures/epilepsy</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No<xref ref-type="table-fn" rid="tfn14-tacg-5-001">e</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Congenital anomalies<xref ref-type="table-fn" rid="tfn15-tacg-5-001">f</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">No<xref ref-type="table-fn" rid="tfn14-tacg-5-001">e</xref></td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td><td align="left" valign="top" rowspan="1" colspan="1">Yes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"><bold>References</bold></td><td align="left" valign="top" rowspan="1" colspan="1">See text<xref ref-type="bibr" rid="b46-tacg-5-001">46</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>, <xref ref-type="bibr" rid="b159-tacg-5-001">159</xref>, <xref ref-type="bibr" rid="b163-tacg-5-001">163</xref>, <xref ref-type="bibr" rid="b164-tacg-5-001">164</xref>, <xref ref-type="bibr" rid="b166-tacg-5-001">166</xref>, <xref ref-type="bibr" rid="b168-tacg-5-001">168</xref>, <xref ref-type="bibr" rid="b170-tacg-5-001">170</xref>, <xref ref-type="bibr" rid="b172-tacg-5-001">172</xref>, <xref ref-type="bibr" rid="b173-tacg-5-001">173</xref>, <xref ref-type="bibr" rid="b175-tacg-5-001">175</xref>, <xref ref-type="bibr" rid="b249-tacg-5-001">249</xref>–<xref ref-type="bibr" rid="b254-tacg-5-001">254</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>, <xref ref-type="bibr" rid="b161-tacg-5-001">161</xref>, <xref ref-type="bibr" rid="b162-tacg-5-001">162</xref>, <xref ref-type="bibr" rid="b166-tacg-5-001">166</xref>, <xref ref-type="bibr" rid="b255-tacg-5-001">255</xref>–<xref ref-type="bibr" rid="b261-tacg-5-001">261</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>, <xref ref-type="bibr" rid="b127-tacg-5-001">127</xref>, <xref ref-type="bibr" rid="b157-tacg-5-001">157</xref>, <xref ref-type="bibr" rid="b159-tacg-5-001">159</xref>, <xref ref-type="bibr" rid="b160-tacg-5-001">160</xref>, <xref ref-type="bibr" rid="b180-tacg-5-001">180</xref>, <xref ref-type="bibr" rid="b262-tacg-5-001">262</xref>–<xref ref-type="bibr" rid="b268-tacg-5-001">268</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>, <xref ref-type="bibr" rid="b159-tacg-5-001">159</xref>–<xref ref-type="bibr" rid="b161-tacg-5-001">161</xref>, <xref ref-type="bibr" rid="b164-tacg-5-001">164</xref>, <xref ref-type="bibr" rid="b166-tacg-5-001">166</xref>, <xref ref-type="bibr" rid="b173-tacg-5-001">173</xref>, <xref ref-type="bibr" rid="b253-tacg-5-001">253</xref>, <xref ref-type="bibr" rid="b254-tacg-5-001">254</xref>, <xref ref-type="bibr" rid="b269-tacg-5-001">269</xref>–<xref ref-type="bibr" rid="b278-tacg-5-001">278</xref></td><td align="left" valign="top" rowspan="1" colspan="1"><xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>, <xref ref-type="bibr" rid="b161-tacg-5-001">161</xref>, <xref ref-type="bibr" rid="b164-tacg-5-001">164</xref>, <xref ref-type="bibr" rid="b166-tacg-5-001">166</xref>, <xref ref-type="bibr" rid="b173-tacg-5-001">173</xref>, <xref ref-type="bibr" rid="b182-tacg-5-001">182</xref>, <xref ref-type="bibr" rid="b253-tacg-5-001">253</xref>, <xref ref-type="bibr" rid="b279-tacg-5-001">279</xref>–<xref ref-type="bibr" rid="b288-tacg-5-001">288</xref></td></tr></tbody></table><table-wrap-foot><fn id="tfn9-tacg-5-001"><p><bold>Notes:</bold></p></fn><fn id="tfn10-tacg-5-001"><label>a</label><p>Originating on maternally derived chromosome;</p></fn><fn id="tfn11-tacg-5-001"><label>b</label><p>there are no pathognomonic signs or symptoms, and the penetrance of each microdeletion or microduplication with respect to each component phenotype is incomplete;</p></fn><fn id="tfn12-tacg-5-001"><label>c</label><p>major depressive disorder, bipolar disorder, attention-deficit hyperactivity disorder/hyperactivity (unspecified), generalized anxiety disorder/anxiety (unspecified), aggression/temper outbursts, and/or major behavior problems (unspecified);</p></fn><fn id="tfn13-tacg-5-001"><label>d</label><p>rare reports only;</p></fn><fn id="tfn14-tacg-5-001"><label>e</label><p>no compelling data as yet, but there remain few detailed reports of the phenotype in individuals with this structural variant;</p></fn><fn id="tfn15-tacg-5-001"><label>f</label><p>cardiac anomalies, palatal anomalies (such as velopharyngeal insufficiency), skeletal abnormalities, and/or other major birth defects.</p></fn><fn id="tfn16-tacg-5-001"><p><bold>Abbreviations:</bold> ASDs, autism spectrum disorders; Mb, mega base pairs; MIM, Mendelian Inheritance in Man.</p></fn></table-wrap-foot></table-wrap><table-wrap id="t4-tacg-5-001" position="float"><label>Table 4</label><caption><p>Pathway to clinical utility for copy number variation and genomic disorders associated with schizophrenia (as of 2011)</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1">Clinically relevant issues</th><th align="left" valign="top" rowspan="1" colspan="1">Established genetic subtype</th><th align="left" valign="top" rowspan="1" colspan="1">Emerging genetic subtypes</th><th align="left" valign="top" rowspan="1" colspan="1">Potential susceptibility factors<xref ref-type="table-fn" rid="tfn18-tacg-5-001">a</xref></th></tr><tr><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1"><hr></hr></th><th align="left" valign="top" rowspan="1" colspan="1"><hr></hr></th><th align="left" valign="top" rowspan="1" colspan="1"><hr></hr></th></tr><tr><th align="left" valign="top" rowspan="1" colspan="1"></th><th align="left" valign="top" rowspan="1" colspan="1">22q11.2 deletion</th><th align="left" valign="top" rowspan="1" colspan="1">1q21.1 deletion<break></break>3q29 deletion<break></break>15q11-q13 duplication<break></break>15q13.3 deletion<break></break>16p11.2 duplication</th><th align="left" valign="top" rowspan="1" colspan="1">Various, including:<break></break>1q21.1 duplication<break></break>15q11.2 deletion<break></break>16p13.11 duplication<break></break>17q12 deletion</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Replication of association in unrelated cohorts</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1">●</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Estimation of population incidence and de novo vs inherited rates</td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn19-tacg-5-001">b</xref></td><td align="center" valign="top" rowspan="1" colspan="1"><xref ref-type="table-fn" rid="tfn20-tacg-5-001">c</xref></td><td align="center" valign="top" rowspan="1" colspan="1"><xref ref-type="table-fn" rid="tfn20-tacg-5-001">c</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Estimation of prevalence within general schizophrenia population</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn21-tacg-5-001">d</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn21-tacg-5-001">d</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Estimation of penetrance for schizophrenia (± for any feature)</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn22-tacg-5-001">e</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn22-tacg-5-001">e</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Assessment of clinical expression of the schizophrenia illness</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Elucidation of neuropsychiatric expression across the lifespan</td><td align="center" valign="top" rowspan="1" colspan="1">●<xref ref-type="table-fn" rid="tfn23-tacg-5-001">f</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn24-tacg-5-001">g</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn24-tacg-5-001">g</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Elucidation of other expression across the lifespan</td><td align="center" valign="top" rowspan="1" colspan="1">●<xref ref-type="table-fn" rid="tfn23-tacg-5-001">f</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn24-tacg-5-001">g</xref></td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn24-tacg-5-001">g</xref></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Search for genetic modifiers of expression</td><td align="center" valign="top" rowspan="1" colspan="1">○</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Search for early clinical predictors of psychosis</td><td align="center" valign="top" rowspan="1" colspan="1">○</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Evaluation of transmission patterns and reproductive fitness</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Development of clinical screening criteria</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Evaluation of prognosis and long-term outcomes</td><td align="center" valign="top" rowspan="1" colspan="1">○</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Identification of opportunities for improved management</td><td align="center" valign="top" rowspan="1" colspan="1">○</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Creation of clinical practice guidelines</td><td align="center" valign="top" rowspan="1" colspan="1">●</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Description of treatment response (pharmacogenomics)</td><td align="center" valign="top" rowspan="1" colspan="1">○<xref ref-type="table-fn" rid="tfn25-tacg-5-001">h</xref></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Identification of specific treatment targets</td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="tfn17-tacg-5-001"><p><bold>Notes:</bold> See text and <xref ref-type="table" rid="t3-tacg-5-001">Table 3</xref> for references.</p></fn><fn id="tfn18-tacg-5-001"><label>a</label><p>Seemingly less penetrant for schizophrenia, and/or with less evidence as yet for association, than the emerging genetic subtypes, see text for details;</p></fn><fn id="tfn19-tacg-5-001"><label>b</label><p>population incidence estimates based mainly on prevalence in infants with major congenital anomalies (eg, congenital heart disease<xref ref-type="bibr" rid="b289-tacg-5-001">289</xref>);<xref ref-type="bibr" rid="b59-tacg-5-001">59</xref></p></fn><fn id="tfn20-tacg-5-001"><label>c</label><p>one nonstandard attempt to estimate the de novo rate using available case-control data;<xref ref-type="bibr" rid="b290-tacg-5-001">290</xref></p></fn><fn id="tfn21-tacg-5-001"><label>d</label><p>estimated from available case-control data;<xref ref-type="bibr" rid="b5-tacg-5-001">5</xref> no studies of consecutive patients, nor any involving only a single centre or community catchment;</p></fn><fn id="tfn22-tacg-5-001"><label>e</label><p>attempts to estimate penetrance did not use standard genetic methods, but instead available case-control data;<xref ref-type="bibr" rid="b64-tacg-5-001">64</xref>,<xref ref-type="bibr" rid="b291-tacg-5-001">291</xref></p></fn><fn id="tfn23-tacg-5-001"><label>f</label><p>adults with 22q11.2DS may have a diminished lifespan;<xref ref-type="bibr" rid="b75-tacg-5-001">75</xref></p></fn><fn id="tfn24-tacg-5-001"><label>g</label><p>some data, primarily derived from association studies of other developmental diseases. Little to no data regarding lifelong expression (ie, in adulthood), or expression in carriers not ascertained through a major phenotype;</p></fn><fn id="tfn25-tacg-5-001"><label>h</label><p>clinical observation suggests that response to treatment is not substantially different in 22q11.2DS-schizophrenia,<xref ref-type="bibr" rid="b9-tacg-5-001">9</xref>,<xref ref-type="bibr" rid="b43-tacg-5-001">43</xref> but there remain limited published data.</p></fn><fn id="tfn26-tacg-5-001"><p>● = Much evidence or progress; ○ = some evidence or progress.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C00 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000C00 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.29. |  |