GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium
Identifieur interne : 000184 ( Pmc/Corpus ); précédent : 000183; suivant : 000185GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium
Auteurs : J W Trampush ; M L Z. Yang ; J. Yu ; E. Knowles ; G. Davies ; D C Liewald ; J M Starr ; S. Djurovic ; I. Melle ; K. Sundet ; A. Christoforou ; I. Reinvang ; P. Derosse ; A J Lundervold ; V M Steen ; T. Espeseth ; K. R Ikkönen ; E. Widen ; A. Palotie ; J G Eriksson ; I. Giegling ; B. Konte ; P. Roussos ; S. Giakoumaki ; K E Burdick ; A. Payton ; W. Ollier ; M. Horan ; O. Chiba-Falek ; D K Attix ; A C Need ; E T Cirulli ; A N Voineskos ; N C Stefanis ; D. Avramopoulos ; A. Hatzimanolis ; D E Arking ; N. Smyrnis ; R M Bilder ; N A Freimer ; T D Cannon ; E. London ; R A Poldrack ; F W Sabb ; E. Congdon ; E D Conley ; M A Scult ; D. Dickinson ; R E Straub ; G. Donohoe ; D. Morris ; A. Corvin ; M. Gill ; A R Hariri ; D R Weinberger ; N. Pendleton ; P. Bitsios ; D. Rujescu ; J. Lahti ; S. Le Hellard ; M C Keller ; O A Andreassen ; I J Deary ; D C Glahn ; A K Malhotra ; T. LenczSource :
- Molecular Psychiatry [ 1359-4184 ] ; 2017.
Abstract
The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the
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DOI: 10.1038/mp.2016.244
PubMed: 28093568
PubMed Central: 5322272
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium</title><author><name sortKey="Trampush, J W" sort="Trampush, J W" uniqKey="Trampush J" first="J W" last="Trampush">J W Trampush</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Yang, M L Z" sort="Yang, M L Z" uniqKey="Yang M" first="M L Z" last="Yang">M L Z. Yang</name><affiliation><nlm:aff id="aff2"><institution>Institute of Mental Health</institution>, Singapore,<country>Singapore</country></nlm:aff></affiliation></author><author><name sortKey="Yu, J" sort="Yu, J" uniqKey="Yu J" first="J" last="Yu">J. Yu</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Knowles, E" sort="Knowles, E" uniqKey="Knowles E" first="E" last="Knowles">E. Knowles</name><affiliation><nlm:aff id="aff4"><institution>Department of Psychiatry, Yale University School of Medicine</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Davies, G" sort="Davies, G" uniqKey="Davies G" first="G" last="Davies">G. Davies</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Liewald, D C" sort="Liewald, D C" uniqKey="Liewald D" first="D C" last="Liewald">D C Liewald</name><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Starr, J M" sort="Starr, J M" uniqKey="Starr J" first="J M" last="Starr">J M Starr</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Alzheimer Scotland Dementia Research Centre, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Djurovic, S" sort="Djurovic, S" uniqKey="Djurovic S" first="S" last="Djurovic">S. Djurovic</name><affiliation><nlm:aff id="aff8"><institution>Department of Medical Genetics, Oslo University Hospital, University of Bergen</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Melle, I" sort="Melle, I" uniqKey="Melle I" first="I" last="Melle">I. Melle</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Sundet, K" sort="Sundet, K" uniqKey="Sundet K" first="K" last="Sundet">K. Sundet</name><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Christoforou, A" sort="Christoforou, A" uniqKey="Christoforou A" first="A" last="Christoforou">A. Christoforou</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Reinvang, I" sort="Reinvang, I" uniqKey="Reinvang I" first="I" last="Reinvang">I. Reinvang</name><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Derosse, P" sort="Derosse, P" uniqKey="Derosse P" first="P" last="Derosse">P. Derosse</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lundervold, A J" sort="Lundervold, A J" uniqKey="Lundervold A" first="A J" last="Lundervold">A J Lundervold</name><affiliation><nlm:aff id="aff13"><institution>Department of Biological and Medical Psychology, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Steen, V M" sort="Steen, V M" uniqKey="Steen V" first="V M" last="Steen">V M Steen</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Espeseth, T" sort="Espeseth, T" uniqKey="Espeseth T" first="T" last="Espeseth">T. Espeseth</name><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="R Ikkonen, K" sort="R Ikkonen, K" uniqKey="R Ikkonen K" first="K" last="R Ikkönen">K. R Ikkönen</name><affiliation><nlm:aff id="aff14"><institution>Institute of Behavioural Sciences, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Widen, E" sort="Widen, E" uniqKey="Widen E" first="E" last="Widen">E. Widen</name><affiliation><nlm:aff id="aff15"><institution>Institute for Molecular Medicine Finland (FIMM), University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Palotie, A" sort="Palotie, A" uniqKey="Palotie A" first="A" last="Palotie">A. Palotie</name><affiliation><nlm:aff id="aff15"><institution>Institute for Molecular Medicine Finland (FIMM), University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution>, Cambridge,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff17"><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Eriksson, J G" sort="Eriksson, J G" uniqKey="Eriksson J" first="J G" last="Eriksson">J G Eriksson</name><affiliation><nlm:aff id="aff18"><institution>National Institute for Health and Welfare</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff19"><institution>Department of General Practice and Primary Health Care, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff20"><institution>Helsinki University Central Hospital, Unit of General Practice</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff21"><institution>Folkhälsan Research Centre</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Giegling, I" sort="Giegling, I" uniqKey="Giegling I" first="I" last="Giegling">I. Giegling</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Konte, B" sort="Konte, B" uniqKey="Konte B" first="B" last="Konte">B. Konte</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Roussos, P" sort="Roussos, P" uniqKey="Roussos P" first="P" last="Roussos">P. Roussos</name><affiliation><nlm:aff id="aff23"><institution>Department of Psychiatry, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><institution>Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff25"><institution>Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center</institution>, Bronx, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Giakoumaki, S" sort="Giakoumaki, S" uniqKey="Giakoumaki S" first="S" last="Giakoumaki">S. Giakoumaki</name><affiliation><nlm:aff id="aff26"><institution>Department of Psychology, University of Crete</institution>, Rethymno,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Burdick, K E" sort="Burdick, K E" uniqKey="Burdick K" first="K E" last="Burdick">K E Burdick</name><affiliation><nlm:aff id="aff23"><institution>Department of Psychiatry, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff25"><institution>Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center</institution>, Bronx, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Payton, A" sort="Payton, A" uniqKey="Payton A" first="A" last="Payton">A. Payton</name><affiliation><nlm:aff id="aff27"><institution>Manchester Centre for Audiology and Deafness, Manchester Academic Health Science Centre, The University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff28"><institution>Division of Evolution and Genomic Sciences, School of Biological Sciences, The University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Ollier, W" sort="Ollier, W" uniqKey="Ollier W" first="W" last="Ollier">W. Ollier</name><affiliation><nlm:aff id="aff29"><institution>Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Horan, M" sort="Horan, M" uniqKey="Horan M" first="M" last="Horan">M. Horan</name><affiliation><nlm:aff id="aff30"><institution>Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Chiba Falek, O" sort="Chiba Falek, O" uniqKey="Chiba Falek O" first="O" last="Chiba-Falek">O. Chiba-Falek</name><affiliation><nlm:aff id="aff31"><institution>Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Attix, D K" sort="Attix, D K" uniqKey="Attix D" first="D K" last="Attix">D K Attix</name><affiliation><nlm:aff id="aff31"><institution>Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff32"><institution>Division of Medical Psychology, Department of Neurology, Psychiatry and Behavioral Sciences, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Need, A C" sort="Need, A C" uniqKey="Need A" first="A C" last="Need">A C Need</name><affiliation><nlm:aff id="aff33"><institution>Division of Brain Sciences, Department of Medicine, Imperial College</institution>, London,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cirulli, E T" sort="Cirulli, E T" uniqKey="Cirulli E" first="E T" last="Cirulli">E T Cirulli</name><affiliation><nlm:aff id="aff34"><institution>Center for Applied Genomics and Precision Medicine, Duke University School of Medicine</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Voineskos, A N" sort="Voineskos, A N" uniqKey="Voineskos A" first="A N" last="Voineskos">A N Voineskos</name><affiliation><nlm:aff id="aff35"><institution>Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto</institution>, Toronto, ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Stefanis, N C" sort="Stefanis, N C" uniqKey="Stefanis N" first="N C" last="Stefanis">N C Stefanis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff38"><institution>Neurobiology Research Institute, Theodor Theohari Cozzika Foundation</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Avramopoulos, D" sort="Avramopoulos, D" uniqKey="Avramopoulos D" first="D" last="Avramopoulos">D. Avramopoulos</name><affiliation><nlm:aff id="aff39"><institution>Department of Psychiatry, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff40"><institution>Department of Psychiatry and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hatzimanolis, A" sort="Hatzimanolis, A" uniqKey="Hatzimanolis A" first="A" last="Hatzimanolis">A. Hatzimanolis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff38"><institution>Neurobiology Research Institute, Theodor Theohari Cozzika Foundation</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Arking, D E" sort="Arking, D E" uniqKey="Arking D" first="D E" last="Arking">D E Arking</name><affiliation><nlm:aff id="aff40"><institution>Department of Psychiatry and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Smyrnis, N" sort="Smyrnis, N" uniqKey="Smyrnis N" first="N" last="Smyrnis">N. Smyrnis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Bilder, R M" sort="Bilder, R M" uniqKey="Bilder R" first="R M" last="Bilder">R M Bilder</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Freimer, N A" sort="Freimer, N A" uniqKey="Freimer N" first="N A" last="Freimer">N A Freimer</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Cannon, T D" sort="Cannon, T D" uniqKey="Cannon T" first="T D" last="Cannon">T D Cannon</name><affiliation><nlm:aff id="aff42"><institution>Department of Psychology, Yale University</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="London, E" sort="London, E" uniqKey="London E" first="E" last="London">E. London</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Poldrack, R A" sort="Poldrack, R A" uniqKey="Poldrack R" first="R A" last="Poldrack">R A Poldrack</name><affiliation><nlm:aff id="aff43"><institution>Department of Psychology, Stanford University</institution>, Palo Alto, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Sabb, F W" sort="Sabb, F W" uniqKey="Sabb F" first="F W" last="Sabb">F W Sabb</name><affiliation><nlm:aff id="aff44"><institution>Robert and Beverly Lewis Center for Neuroimaging, University of Oregon</institution>, Eugene, OR,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Congdon, E" sort="Congdon, E" uniqKey="Congdon E" first="E" last="Congdon">E. Congdon</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Conley, E D" sort="Conley, E D" uniqKey="Conley E" first="E D" last="Conley">E D Conley</name><affiliation><nlm:aff id="aff45"><institution>23andMe, Inc.</institution>, Mountain View, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Scult, M A" sort="Scult, M A" uniqKey="Scult M" first="M A" last="Scult">M A Scult</name><affiliation><nlm:aff id="aff46"><institution>Department of Psychology & Neuroscience, Laboratory of NeuroGenetics, Duke University</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Dickinson, D" sort="Dickinson, D" uniqKey="Dickinson D" first="D" last="Dickinson">D. Dickinson</name><affiliation><nlm:aff id="aff47"><institution>Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health</institution>, Bethesda, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Straub, R E" sort="Straub, R E" uniqKey="Straub R" first="R E" last="Straub">R E Straub</name><affiliation><nlm:aff id="aff48"><institution>Lieber Institute for Brain Development, Johns Hopkins University Medical Campus</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Donohoe, G" sort="Donohoe, G" uniqKey="Donohoe G" first="G" last="Donohoe">G. Donohoe</name><affiliation><nlm:aff id="aff49"><institution>Department of Psychology, National University of Ireland</institution>, Galway,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Morris, D" sort="Morris, D" uniqKey="Morris D" first="D" last="Morris">D. Morris</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Corvin, A" sort="Corvin, A" uniqKey="Corvin A" first="A" last="Corvin">A. Corvin</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Gill, M" sort="Gill, M" uniqKey="Gill M" first="M" last="Gill">M. Gill</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Hariri, A R" sort="Hariri, A R" uniqKey="Hariri A" first="A R" last="Hariri">A R Hariri</name><affiliation><nlm:aff id="aff46"><institution>Department of Psychology & Neuroscience, Laboratory of NeuroGenetics, Duke University</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Weinberger, D R" sort="Weinberger, D R" uniqKey="Weinberger D" first="D R" last="Weinberger">D R Weinberger</name><affiliation><nlm:aff id="aff48"><institution>Lieber Institute for Brain Development, Johns Hopkins University Medical Campus</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Pendleton, N" sort="Pendleton, N" uniqKey="Pendleton N" first="N" last="Pendleton">N. Pendleton</name><affiliation><nlm:aff id="aff29"><institution>Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff30"><institution>Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Bitsios, P" sort="Bitsios, P" uniqKey="Bitsios P" first="P" last="Bitsios">P. Bitsios</name><affiliation><nlm:aff id="aff51"><institution>Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete</institution>, Heraklion,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Rujescu, D" sort="Rujescu, D" uniqKey="Rujescu D" first="D" last="Rujescu">D. Rujescu</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Lahti, J" sort="Lahti, J" uniqKey="Lahti J" first="J" last="Lahti">J. Lahti</name><affiliation><nlm:aff id="aff14"><institution>Institute of Behavioural Sciences, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff52"><institution>Helsinki Collegium for Advanced Studies, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Le Hellard, S" sort="Le Hellard, S" uniqKey="Le Hellard S" first="S" last="Le Hellard">S. Le Hellard</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Keller, M C" sort="Keller, M C" uniqKey="Keller M" first="M C" last="Keller">M C Keller</name><affiliation><nlm:aff id="aff53"><institution>Institute for Behavioral Genetics, University of Colorado</institution>, Boulder,<country>CO, USA</country></nlm:aff></affiliation></author><author><name sortKey="Andreassen, O A" sort="Andreassen, O A" uniqKey="Andreassen O" first="O A" last="Andreassen">O A Andreassen</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff54"><institution>Institute of Clinical Medicine, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Deary, I J" sort="Deary, I J" uniqKey="Deary I" first="I J" last="Deary">I J Deary</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Glahn, D C" sort="Glahn, D C" uniqKey="Glahn D" first="D C" last="Glahn">D C Glahn</name><affiliation><nlm:aff id="aff4"><institution>Department of Psychiatry, Yale University School of Medicine</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Malhotra, A K" sort="Malhotra, A K" uniqKey="Malhotra A" first="A K" last="Malhotra">A K Malhotra</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff55"><institution>Department of Psychiatry, Hofstra Northwell School of Medicine</institution>, Hempstead, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lencz, T" sort="Lencz, T" uniqKey="Lencz T" first="T" last="Lencz">T. Lencz</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff55"><institution>Department of Psychiatry, Hofstra Northwell School of Medicine</institution>, Hempstead, NY,<country>USA</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28093568</idno><idno type="pmc">5322272</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322272</idno><idno type="RBID">PMC:5322272</idno><idno type="doi">10.1038/mp.2016.244</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000184</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000184</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium</title><author><name sortKey="Trampush, J W" sort="Trampush, J W" uniqKey="Trampush J" first="J W" last="Trampush">J W Trampush</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Yang, M L Z" sort="Yang, M L Z" uniqKey="Yang M" first="M L Z" last="Yang">M L Z. Yang</name><affiliation><nlm:aff id="aff2"><institution>Institute of Mental Health</institution>, Singapore,<country>Singapore</country></nlm:aff></affiliation></author><author><name sortKey="Yu, J" sort="Yu, J" uniqKey="Yu J" first="J" last="Yu">J. Yu</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Knowles, E" sort="Knowles, E" uniqKey="Knowles E" first="E" last="Knowles">E. Knowles</name><affiliation><nlm:aff id="aff4"><institution>Department of Psychiatry, Yale University School of Medicine</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Davies, G" sort="Davies, G" uniqKey="Davies G" first="G" last="Davies">G. Davies</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Liewald, D C" sort="Liewald, D C" uniqKey="Liewald D" first="D C" last="Liewald">D C Liewald</name><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Starr, J M" sort="Starr, J M" uniqKey="Starr J" first="J M" last="Starr">J M Starr</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff7"><institution>Alzheimer Scotland Dementia Research Centre, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Djurovic, S" sort="Djurovic, S" uniqKey="Djurovic S" first="S" last="Djurovic">S. Djurovic</name><affiliation><nlm:aff id="aff8"><institution>Department of Medical Genetics, Oslo University Hospital, University of Bergen</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Melle, I" sort="Melle, I" uniqKey="Melle I" first="I" last="Melle">I. Melle</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Sundet, K" sort="Sundet, K" uniqKey="Sundet K" first="K" last="Sundet">K. Sundet</name><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Christoforou, A" sort="Christoforou, A" uniqKey="Christoforou A" first="A" last="Christoforou">A. Christoforou</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Reinvang, I" sort="Reinvang, I" uniqKey="Reinvang I" first="I" last="Reinvang">I. Reinvang</name><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Derosse, P" sort="Derosse, P" uniqKey="Derosse P" first="P" last="Derosse">P. Derosse</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lundervold, A J" sort="Lundervold, A J" uniqKey="Lundervold A" first="A J" last="Lundervold">A J Lundervold</name><affiliation><nlm:aff id="aff13"><institution>Department of Biological and Medical Psychology, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Steen, V M" sort="Steen, V M" uniqKey="Steen V" first="V M" last="Steen">V M Steen</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Espeseth, T" sort="Espeseth, T" uniqKey="Espeseth T" first="T" last="Espeseth">T. Espeseth</name><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff11"><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="R Ikkonen, K" sort="R Ikkonen, K" uniqKey="R Ikkonen K" first="K" last="R Ikkönen">K. R Ikkönen</name><affiliation><nlm:aff id="aff14"><institution>Institute of Behavioural Sciences, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Widen, E" sort="Widen, E" uniqKey="Widen E" first="E" last="Widen">E. Widen</name><affiliation><nlm:aff id="aff15"><institution>Institute for Molecular Medicine Finland (FIMM), University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Palotie, A" sort="Palotie, A" uniqKey="Palotie A" first="A" last="Palotie">A. Palotie</name><affiliation><nlm:aff id="aff15"><institution>Institute for Molecular Medicine Finland (FIMM), University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff16"><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution>, Cambridge,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff17"><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Eriksson, J G" sort="Eriksson, J G" uniqKey="Eriksson J" first="J G" last="Eriksson">J G Eriksson</name><affiliation><nlm:aff id="aff18"><institution>National Institute for Health and Welfare</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff19"><institution>Department of General Practice and Primary Health Care, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff20"><institution>Helsinki University Central Hospital, Unit of General Practice</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff21"><institution>Folkhälsan Research Centre</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Giegling, I" sort="Giegling, I" uniqKey="Giegling I" first="I" last="Giegling">I. Giegling</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Konte, B" sort="Konte, B" uniqKey="Konte B" first="B" last="Konte">B. Konte</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Roussos, P" sort="Roussos, P" uniqKey="Roussos P" first="P" last="Roussos">P. Roussos</name><affiliation><nlm:aff id="aff23"><institution>Department of Psychiatry, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff24"><institution>Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff25"><institution>Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center</institution>, Bronx, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Giakoumaki, S" sort="Giakoumaki, S" uniqKey="Giakoumaki S" first="S" last="Giakoumaki">S. Giakoumaki</name><affiliation><nlm:aff id="aff26"><institution>Department of Psychology, University of Crete</institution>, Rethymno,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Burdick, K E" sort="Burdick, K E" uniqKey="Burdick K" first="K E" last="Burdick">K E Burdick</name><affiliation><nlm:aff id="aff23"><institution>Department of Psychiatry, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff25"><institution>Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center</institution>, Bronx, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Payton, A" sort="Payton, A" uniqKey="Payton A" first="A" last="Payton">A. Payton</name><affiliation><nlm:aff id="aff27"><institution>Manchester Centre for Audiology and Deafness, Manchester Academic Health Science Centre, The University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff28"><institution>Division of Evolution and Genomic Sciences, School of Biological Sciences, The University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Ollier, W" sort="Ollier, W" uniqKey="Ollier W" first="W" last="Ollier">W. Ollier</name><affiliation><nlm:aff id="aff29"><institution>Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Horan, M" sort="Horan, M" uniqKey="Horan M" first="M" last="Horan">M. Horan</name><affiliation><nlm:aff id="aff30"><institution>Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Chiba Falek, O" sort="Chiba Falek, O" uniqKey="Chiba Falek O" first="O" last="Chiba-Falek">O. Chiba-Falek</name><affiliation><nlm:aff id="aff31"><institution>Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Attix, D K" sort="Attix, D K" uniqKey="Attix D" first="D K" last="Attix">D K Attix</name><affiliation><nlm:aff id="aff31"><institution>Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff32"><institution>Division of Medical Psychology, Department of Neurology, Psychiatry and Behavioral Sciences, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Need, A C" sort="Need, A C" uniqKey="Need A" first="A C" last="Need">A C Need</name><affiliation><nlm:aff id="aff33"><institution>Division of Brain Sciences, Department of Medicine, Imperial College</institution>, London,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Cirulli, E T" sort="Cirulli, E T" uniqKey="Cirulli E" first="E T" last="Cirulli">E T Cirulli</name><affiliation><nlm:aff id="aff34"><institution>Center for Applied Genomics and Precision Medicine, Duke University School of Medicine</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Voineskos, A N" sort="Voineskos, A N" uniqKey="Voineskos A" first="A N" last="Voineskos">A N Voineskos</name><affiliation><nlm:aff id="aff35"><institution>Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto</institution>, Toronto, ON,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Stefanis, N C" sort="Stefanis, N C" uniqKey="Stefanis N" first="N C" last="Stefanis">N C Stefanis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff38"><institution>Neurobiology Research Institute, Theodor Theohari Cozzika Foundation</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Avramopoulos, D" sort="Avramopoulos, D" uniqKey="Avramopoulos D" first="D" last="Avramopoulos">D. Avramopoulos</name><affiliation><nlm:aff id="aff39"><institution>Department of Psychiatry, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff40"><institution>Department of Psychiatry and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Hatzimanolis, A" sort="Hatzimanolis, A" uniqKey="Hatzimanolis A" first="A" last="Hatzimanolis">A. Hatzimanolis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff38"><institution>Neurobiology Research Institute, Theodor Theohari Cozzika Foundation</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Arking, D E" sort="Arking, D E" uniqKey="Arking D" first="D E" last="Arking">D E Arking</name><affiliation><nlm:aff id="aff40"><institution>Department of Psychiatry and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Smyrnis, N" sort="Smyrnis, N" uniqKey="Smyrnis N" first="N" last="Smyrnis">N. Smyrnis</name><affiliation><nlm:aff id="aff36"><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff37"><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Bilder, R M" sort="Bilder, R M" uniqKey="Bilder R" first="R M" last="Bilder">R M Bilder</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Freimer, N A" sort="Freimer, N A" uniqKey="Freimer N" first="N A" last="Freimer">N A Freimer</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Cannon, T D" sort="Cannon, T D" uniqKey="Cannon T" first="T D" last="Cannon">T D Cannon</name><affiliation><nlm:aff id="aff42"><institution>Department of Psychology, Yale University</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="London, E" sort="London, E" uniqKey="London E" first="E" last="London">E. London</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Poldrack, R A" sort="Poldrack, R A" uniqKey="Poldrack R" first="R A" last="Poldrack">R A Poldrack</name><affiliation><nlm:aff id="aff43"><institution>Department of Psychology, Stanford University</institution>, Palo Alto, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Sabb, F W" sort="Sabb, F W" uniqKey="Sabb F" first="F W" last="Sabb">F W Sabb</name><affiliation><nlm:aff id="aff44"><institution>Robert and Beverly Lewis Center for Neuroimaging, University of Oregon</institution>, Eugene, OR,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Congdon, E" sort="Congdon, E" uniqKey="Congdon E" first="E" last="Congdon">E. Congdon</name><affiliation><nlm:aff id="aff41"><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Conley, E D" sort="Conley, E D" uniqKey="Conley E" first="E D" last="Conley">E D Conley</name><affiliation><nlm:aff id="aff45"><institution>23andMe, Inc.</institution>, Mountain View, CA,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Scult, M A" sort="Scult, M A" uniqKey="Scult M" first="M A" last="Scult">M A Scult</name><affiliation><nlm:aff id="aff46"><institution>Department of Psychology & Neuroscience, Laboratory of NeuroGenetics, Duke University</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Dickinson, D" sort="Dickinson, D" uniqKey="Dickinson D" first="D" last="Dickinson">D. Dickinson</name><affiliation><nlm:aff id="aff47"><institution>Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health</institution>, Bethesda, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Straub, R E" sort="Straub, R E" uniqKey="Straub R" first="R E" last="Straub">R E Straub</name><affiliation><nlm:aff id="aff48"><institution>Lieber Institute for Brain Development, Johns Hopkins University Medical Campus</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Donohoe, G" sort="Donohoe, G" uniqKey="Donohoe G" first="G" last="Donohoe">G. Donohoe</name><affiliation><nlm:aff id="aff49"><institution>Department of Psychology, National University of Ireland</institution>, Galway,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Morris, D" sort="Morris, D" uniqKey="Morris D" first="D" last="Morris">D. Morris</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Corvin, A" sort="Corvin, A" uniqKey="Corvin A" first="A" last="Corvin">A. Corvin</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Gill, M" sort="Gill, M" uniqKey="Gill M" first="M" last="Gill">M. Gill</name><affiliation><nlm:aff id="aff50"><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></nlm:aff></affiliation></author><author><name sortKey="Hariri, A R" sort="Hariri, A R" uniqKey="Hariri A" first="A R" last="Hariri">A R Hariri</name><affiliation><nlm:aff id="aff46"><institution>Department of Psychology & Neuroscience, Laboratory of NeuroGenetics, Duke University</institution>, Durham, NC,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Weinberger, D R" sort="Weinberger, D R" uniqKey="Weinberger D" first="D R" last="Weinberger">D R Weinberger</name><affiliation><nlm:aff id="aff48"><institution>Lieber Institute for Brain Development, Johns Hopkins University Medical Campus</institution>, Baltimore, MD,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Pendleton, N" sort="Pendleton, N" uniqKey="Pendleton N" first="N" last="Pendleton">N. Pendleton</name><affiliation><nlm:aff id="aff29"><institution>Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff30"><institution>Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester</institution>, Manchester,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Bitsios, P" sort="Bitsios, P" uniqKey="Bitsios P" first="P" last="Bitsios">P. Bitsios</name><affiliation><nlm:aff id="aff51"><institution>Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete</institution>, Heraklion,<country>Greece</country></nlm:aff></affiliation></author><author><name sortKey="Rujescu, D" sort="Rujescu, D" uniqKey="Rujescu D" first="D" last="Rujescu">D. Rujescu</name><affiliation><nlm:aff id="aff22"><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></nlm:aff></affiliation></author><author><name sortKey="Lahti, J" sort="Lahti, J" uniqKey="Lahti J" first="J" last="Lahti">J. Lahti</name><affiliation><nlm:aff id="aff14"><institution>Institute of Behavioural Sciences, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff52"><institution>Helsinki Collegium for Advanced Studies, University of Helsinki</institution>, Helsinki,<country>Finland</country></nlm:aff></affiliation></author><author><name sortKey="Le Hellard, S" sort="Le Hellard, S" uniqKey="Le Hellard S" first="S" last="Le Hellard">S. Le Hellard</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff12"><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Keller, M C" sort="Keller, M C" uniqKey="Keller M" first="M C" last="Keller">M C Keller</name><affiliation><nlm:aff id="aff53"><institution>Institute for Behavioral Genetics, University of Colorado</institution>, Boulder,<country>CO, USA</country></nlm:aff></affiliation></author><author><name sortKey="Andreassen, O A" sort="Andreassen, O A" uniqKey="Andreassen O" first="O A" last="Andreassen">O A Andreassen</name><affiliation><nlm:aff id="aff9"><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff10"><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff54"><institution>Institute of Clinical Medicine, University of Oslo</institution>, Oslo,<country>Norway</country></nlm:aff></affiliation></author><author><name sortKey="Deary, I J" sort="Deary, I J" uniqKey="Deary I" first="I J" last="Deary">I J Deary</name><affiliation><nlm:aff id="aff5"><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff6"><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Glahn, D C" sort="Glahn, D C" uniqKey="Glahn D" first="D C" last="Glahn">D C Glahn</name><affiliation><nlm:aff id="aff4"><institution>Department of Psychiatry, Yale University School of Medicine</institution>, New Haven, CT,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Malhotra, A K" sort="Malhotra, A K" uniqKey="Malhotra A" first="A K" last="Malhotra">A K Malhotra</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff55"><institution>Department of Psychiatry, Hofstra Northwell School of Medicine</institution>, Hempstead, NY,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Lencz, T" sort="Lencz, T" uniqKey="Lencz T" first="T" last="Lencz">T. Lencz</name><affiliation><nlm:aff id="aff1"><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff55"><institution>Department of Psychiatry, Hofstra Northwell School of Medicine</institution>, Hempstead, NY,<country>USA</country></nlm:aff></affiliation></author></analytic><series><title level="j">Molecular Psychiatry</title><idno type="ISSN">1359-4184</idno><idno type="eISSN">1476-5578</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the <italic>CENPO</italic> gene on chromosome 2 and rs6669072 near <italic>LOC105378853</italic> on chromosome 1) associated with cognitive performance at the genome-wide significance level (<italic>P</italic><5 × 10<sup>−8</sup>). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="rapid-communication"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Psychiatry</journal-id><journal-id journal-id-type="iso-abbrev">Mol. Psychiatry</journal-id><journal-title-group><journal-title>Molecular Psychiatry</journal-title></journal-title-group><issn pub-type="ppub">1359-4184</issn><issn pub-type="epub">1476-5578</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28093568</article-id><article-id pub-id-type="pmc">5322272</article-id><article-id pub-id-type="pii">mp2016244</article-id><article-id pub-id-type="doi">10.1038/mp.2016.244</article-id><article-categories><subj-group subj-group-type="heading"><subject>Immediate Communication</subject></subj-group></article-categories><title-group><article-title>GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium</article-title><alt-title alt-title-type="running">GWAS of general cognitive function</alt-title></title-group><contrib-group><contrib 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rid="aff10">10</xref><xref ref-type="aff" rid="aff54">54</xref></contrib><contrib contrib-type="author"><name><surname>Deary</surname><given-names>I J</given-names></name><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Glahn</surname><given-names>D C</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Malhotra</surname><given-names>A K</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff55">55</xref></contrib><contrib contrib-type="author"><name><surname>Lencz</surname><given-names>T</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff55">55</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, Glen Oaks, NY,<country>USA</country></aff><aff id="aff2"><label>2</label><institution>Institute of Mental Health</institution>, Singapore,<country>Singapore</country></aff><aff id="aff3"><label>3</label><institution>Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research</institution>, Manhasset, NY,<country>USA</country></aff><aff id="aff4"><label>4</label><institution>Department of Psychiatry, Yale University School of Medicine</institution>, New Haven, CT,<country>USA</country></aff><aff id="aff5"><label>5</label><institution>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></aff><aff id="aff6"><label>6</label><institution>Department of Psychology, University of Edinburgh</institution>, Edinburgh,<country>UK</country></aff><aff id="aff7"><label>7</label><institution>Alzheimer Scotland Dementia Research Centre, University of Edinburgh</institution>, Edinburgh,<country>UK</country></aff><aff id="aff8"><label>8</label><institution>Department of Medical Genetics, Oslo University Hospital, University of Bergen</institution>, Oslo,<country>Norway</country></aff><aff id="aff9"><label>9</label><institution>NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen</institution>, Bergen,<country>Norway</country></aff><aff id="aff10"><label>10</label><institution>Division of Mental Health and Addiction, Oslo University Hospital</institution>, Oslo,<country>Norway</country></aff><aff id="aff11"><label>11</label><institution>Department of Psychology, University of Oslo</institution>, Oslo,<country>Norway</country></aff><aff id="aff12"><label>12</label><institution>Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</institution>, Bergen,<country>Norway</country></aff><aff id="aff13"><label>13</label><institution>Department of Biological and Medical Psychology, University of Bergen</institution>, Bergen,<country>Norway</country></aff><aff id="aff14"><label>14</label><institution>Institute of Behavioural Sciences, University of Helsinki</institution>, Helsinki,<country>Finland</country></aff><aff id="aff15"><label>15</label><institution>Institute for Molecular Medicine Finland (FIMM), University of Helsinki</institution>, Helsinki,<country>Finland</country></aff><aff id="aff16"><label>16</label><institution>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus</institution>, Cambridge,<country>UK</country></aff><aff id="aff17"><label>17</label><institution>Department of Medical Genetics, University of Helsinki and University Central Hospital</institution>, Helsinki,<country>Finland</country></aff><aff id="aff18"><label>18</label><institution>National Institute for Health and Welfare</institution>, Helsinki,<country>Finland</country></aff><aff id="aff19"><label>19</label><institution>Department of General Practice and Primary Health Care, University of Helsinki</institution>, Helsinki,<country>Finland</country></aff><aff id="aff20"><label>20</label><institution>Helsinki University Central Hospital, Unit of General Practice</institution>, Helsinki,<country>Finland</country></aff><aff id="aff21"><label>21</label><institution>Folkhälsan Research Centre</institution>, Helsinki,<country>Finland</country></aff><aff id="aff22"><label>22</label><institution>Department of Psychiatry, Martin Luther University of Halle-Wittenberg</institution>, Halle,<country>Germany</country></aff><aff id="aff23"><label>23</label><institution>Department of Psychiatry, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></aff><aff id="aff24"><label>24</label><institution>Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai</institution>, New York, NY,<country>USA</country></aff><aff id="aff25"><label>25</label><institution>Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center</institution>, Bronx, NY,<country>USA</country></aff><aff id="aff26"><label>26</label><institution>Department of Psychology, University of Crete</institution>, Rethymno,<country>Greece</country></aff><aff id="aff27"><label>27</label><institution>Manchester Centre for Audiology and Deafness, Manchester Academic Health Science Centre, The University of Manchester</institution>, Manchester,<country>UK</country></aff><aff id="aff28"><label>28</label><institution>Division of Evolution and Genomic Sciences, School of Biological Sciences, The University of Manchester</institution>, Manchester,<country>UK</country></aff><aff id="aff29"><label>29</label><institution>Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester</institution>, Manchester,<country>UK</country></aff><aff id="aff30"><label>30</label><institution>Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester</institution>, Manchester,<country>UK</country></aff><aff id="aff31"><label>31</label><institution>Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></aff><aff id="aff32"><label>32</label><institution>Division of Medical Psychology, Department of Neurology, Psychiatry and Behavioral Sciences, Duke University Medical Center</institution>, Durham, NC,<country>USA</country></aff><aff id="aff33"><label>33</label><institution>Division of Brain Sciences, Department of Medicine, Imperial College</institution>, London,<country>UK</country></aff><aff id="aff34"><label>34</label><institution>Center for Applied Genomics and Precision Medicine, Duke University School of Medicine</institution>, Durham, NC,<country>USA</country></aff><aff id="aff35"><label>35</label><institution>Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto</institution>, Toronto, ON,<country>Canada</country></aff><aff id="aff36"><label>36</label><institution>Department of Psychiatry, University of Athens School of Medicine, Eginition Hospital</institution>, Athens,<country>Greece</country></aff><aff id="aff37"><label>37</label><institution>University Mental Health Research Institute</institution>, Athens,<country>Greece</country></aff><aff id="aff38"><label>38</label><institution>Neurobiology Research Institute, Theodor Theohari Cozzika Foundation</institution>, Athens,<country>Greece</country></aff><aff id="aff39"><label>39</label><institution>Department of Psychiatry, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></aff><aff id="aff40"><label>40</label><institution>Department of Psychiatry and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine</institution>, Baltimore, MD,<country>USA</country></aff><aff id="aff41"><label>41</label><institution>UCLA Semel Institute for Neuroscience and Human Behavior</institution>, Los Angeles, CA,<country>USA</country></aff><aff id="aff42"><label>42</label><institution>Department of Psychology, Yale University</institution>, New Haven, CT,<country>USA</country></aff><aff id="aff43"><label>43</label><institution>Department of Psychology, Stanford University</institution>, Palo Alto, CA,<country>USA</country></aff><aff id="aff44"><label>44</label><institution>Robert and Beverly Lewis Center for Neuroimaging, University of Oregon</institution>, Eugene, OR,<country>USA</country></aff><aff id="aff45"><label>45</label><institution>23andMe, Inc.</institution>, Mountain View, CA,<country>USA</country></aff><aff id="aff46"><label>46</label><institution>Department of Psychology & Neuroscience, Laboratory of NeuroGenetics, Duke University</institution>, Durham, NC,<country>USA</country></aff><aff id="aff47"><label>47</label><institution>Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health</institution>, Bethesda, MD,<country>USA</country></aff><aff id="aff48"><label>48</label><institution>Lieber Institute for Brain Development, Johns Hopkins University Medical Campus</institution>, Baltimore, MD,<country>USA</country></aff><aff id="aff49"><label>49</label><institution>Department of Psychology, National University of Ireland</institution>, Galway,<country>Ireland</country></aff><aff id="aff50"><label>50</label><institution>Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Institute of Neuroscience, Trinity College Dublin</institution>, Dublin,<country>Ireland</country></aff><aff id="aff51"><label>51</label><institution>Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete</institution>, Heraklion,<country>Greece</country></aff><aff id="aff52"><label>52</label><institution>Helsinki Collegium for Advanced Studies, University of Helsinki</institution>, Helsinki,<country>Finland</country></aff><aff id="aff53"><label>53</label><institution>Institute for Behavioral Genetics, University of Colorado</institution>, Boulder,<country>CO, USA</country></aff><aff id="aff54"><label>54</label><institution>Institute of Clinical Medicine, University of Oslo</institution>, Oslo,<country>Norway</country></aff><aff id="aff55"><label>55</label><institution>Department of Psychiatry, Hofstra Northwell School of Medicine</institution>, Hempstead, NY,<country>USA</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>Division of Psychiatry Research, Zucker Hillside Hospital</institution>, 75-59 263rd Street, Glen Oaks, NY 11004, <country>USA</country>. E-mail: <email>tlencz@northwell.edu</email></corresp><fn fn-type="present-address" id="note1"><label>56</label><p>These two authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><month>03</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>17</day><month>01</month><year>2017</year></pub-date><volume>22</volume><issue>3</issue><fpage>336</fpage><lpage>345</lpage><history><date date-type="received"><day>12</day><month>09</month><year>2016</year></date><date date-type="rev-recd"><day>30</day><month>10</month><year>2016</year></date><date date-type="accepted"><day>03</day><month>11</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2017 The Author(s)</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the <italic>CENPO</italic> gene on chromosome 2 and rs6669072 near <italic>LOC105378853</italic> on chromosome 1) associated with cognitive performance at the genome-wide significance level (<italic>P</italic><5 × 10<sup>−8</sup>). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.</p></abstract></article-meta></front><body><sec><title>Introduction</title><p>Genome-wide association studies (GWAS) of complex quantitative phenotypes such as height<sup><xref ref-type="bibr" rid="bib1">1</xref></sup> and body mass index<sup><xref ref-type="bibr" rid="bib2">2</xref></sup> have successfully discovered and replicated hundreds of common variants meeting criteria for genome-wide significant association. By contrast, finding genetic loci associated with individual differences in cognitive ability using GWAS has proven challenging, despite considerable evidence from family and twin studies indicating that cognitive ability is highly heritable.<sup><xref ref-type="bibr" rid="bib3">3</xref></sup> For example, no genome-wide significant hits were detected in the earliest multi-cohort GWAS meta-analyses of general cognitive ability in ~3500 adults,<sup><xref ref-type="bibr" rid="bib4">4</xref></sup> or in ~5000 adults,<sup><xref ref-type="bibr" rid="bib5">5</xref></sup> or in ~18 000 youth.<sup><xref ref-type="bibr" rid="bib6">6</xref></sup> However, the first results attaining genome-wide significance, in three loci on chromosomes 6, 14 and 19, recently emerged in a GWAS meta-analysis of general cognitive function in 53 949 adults reported by the CHARGE Consortium.<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> In addition, a recent study using data collected as part of the UK Biobank project reported three genomic regions significantly associated with performance on a test of verbal numerical reasoning (<italic>N</italic>=36 035), and two independent loci were significantly associated with performance on a reaction time task (<italic>N</italic>=111 483).<sup><xref ref-type="bibr" rid="bib8">8</xref></sup> However, in the same cohort, no genome-wide significant single-nucleotide polymorphisms (SNP)-based findings were detected for scores on a memory test, despite the large sample size (<italic>N</italic>=112 067), perhaps due to the low reliability of the very brief assay available.<sup><xref ref-type="bibr" rid="bib8">8</xref></sup></p><p>Recent GWAS meta-analyses of educational attainment, proposed as a proxy phenotype for cognition,<sup><xref ref-type="bibr" rid="bib8">8</xref>, <xref ref-type="bibr" rid="bib9">9</xref>, <xref ref-type="bibr" rid="bib10">10</xref>, <xref ref-type="bibr" rid="bib11">11</xref>, <xref ref-type="bibr" rid="bib12">12</xref></sup> have demonstrated that associations can be discovered with sufficient sample size, with the most recent analysis of 293 723 individuals yielding 74 independent SNPs that reached genome-wide significance.<sup><xref ref-type="bibr" rid="bib9">9</xref></sup> Nevertheless, this number of hits is an order of magnitude smaller than that reported for a similarly powered GWAS meta-analysis of height, which identified 697 variants that together explained ~16% of the variance for adult height in a sample of 253 288 individuals.<sup><xref ref-type="bibr" rid="bib1">1</xref></sup> Thus, the complex nature of human cognition, exacerbated by challenges of precise and reliable measurement, has rendered it a more difficult phenotype with which to gain traction in the era of GWAS discovery.</p><p>The importance of uncovering the molecular genetic basis of cognitive functioning is underscored by the fact that neurocognitive deficits represent a critical component of many neuropsychiatric disorders and disease states that can affect health outcomes across the lifespan. As examples, most early appearing neurodevelopmental disorders such as autism spectrum disorder<sup><xref ref-type="bibr" rid="bib13">13</xref></sup> and attention-deficit/hyperactivity disorder<sup><xref ref-type="bibr" rid="bib14">14</xref></sup> are associated with moderate to relatively impairing comorbid deficits in neurocognitive functioning. Longitudinally, lower cognitive ability scores in childhood have been linked to decreased rates of smoking cessation in adulthood.<sup><xref ref-type="bibr" rid="bib15">15</xref></sup> The major neuropsychiatric disorders that typically emerge in early adulthood, such as schizophrenia,<sup><xref ref-type="bibr" rid="bib16">16</xref></sup> bipolar disorder,<sup><xref ref-type="bibr" rid="bib17">17</xref></sup> anxiety disorders<sup><xref ref-type="bibr" rid="bib18">18</xref></sup> and depression,<sup><xref ref-type="bibr" rid="bib19">19</xref></sup> are also associated with a range of deficits in neurocognitive function. Human personality traits such as openness to new experiences<sup><xref ref-type="bibr" rid="bib20">20</xref></sup> and negative affect<sup><xref ref-type="bibr" rid="bib21">21</xref></sup> are, respectively, associated with better and worse neurocognitive performance. Individuals with debilitating neurological illnesses such as Parkinson's disease<sup><xref ref-type="bibr" rid="bib22">22</xref>, <xref ref-type="bibr" rid="bib23">23</xref></sup> and (by definition) the dementia spectrum including Alzheimer's disease<sup><xref ref-type="bibr" rid="bib24">24</xref></sup> also suffer from marked neurocognitive impairments. Further, early life cognitive performance can predict long-term development of illness,<sup><xref ref-type="bibr" rid="bib25">25</xref></sup> including mortality.<sup><xref ref-type="bibr" rid="bib26">26</xref></sup> From these findings, it has been suggested that general cognitive performance may index global bodily integrity, thereby permitting a potentially broad application of ‘cognitive epidemiology.'<sup><xref ref-type="bibr" rid="bib27">27</xref></sup></p><p>Deciphering the genetic overlap between cognition and risk for neuropsychiatric illness and other health-relevant traits can provide useful etiological insights and help prioritize likely causal relationships among complex human traits.<sup><xref ref-type="bibr" rid="bib28">28</xref></sup> Methods to estimate the genome-wide genetic correlation (<italic>r</italic><sub>g</sub>) between two traits using summary GWAS statistics from published research studies utilizing linkage disequilibrium (LD) score regression procedures have recently become available.<sup><xref ref-type="bibr" rid="bib28">28</xref>, <xref ref-type="bibr" rid="bib29">29</xref></sup> LD score regression has been used recently to show significant genetic correlations between cognition-related phenotypes and cardiovascular disease,<sup><xref ref-type="bibr" rid="bib27">27</xref></sup> physical health<sup><xref ref-type="bibr" rid="bib30">30</xref></sup> and neuropsychiatric illness.<sup><xref ref-type="bibr" rid="bib31">31</xref></sup> However, the underlying causal variants and the genes through which they act have yet to be identified.<sup><xref ref-type="bibr" rid="bib32">32</xref></sup></p><p>There were two major aims of the current study: (1) conduct a large-scale (<italic>n</italic>=35 298) GWAS meta-analysis of general cognitive function in 24 independent cohorts, to identify SNP-based and gene-based loci associated with cognition; and (2) determine the extent of genetic correlation between general cognitive function and published neurobehavioral phenotypes of interest. These aims were executed within the context of the Cognitive Genomics Consortium (COGENT),<sup><xref ref-type="bibr" rid="bib5">5</xref>, <xref ref-type="bibr" rid="bib10">10</xref></sup> an international collaborative effort designed to study the molecular genetics of cognitive function.</p></sec><sec><title>Materials and methods</title><sec><title>Participants</title><p>To date, COGENT has acquired individual-level neuropsychological, demographic, clinical and SNP array data from 24 studies (comprised of 35 sub-studies) enrolling 35 298 individuals (51.4% females, mean age of 45.6 (s.d.±8.6) years) of European ancestry drawn from the general population in North America, the United Kingdom and the European continent. <xref rid="tbl1" ref-type="table">Table 1</xref> provides details of the individual study cohorts. A few of the cohorts overlap with those previously reported by the CHARGE consortium,<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> so comparisons to the CHARGE report<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> utilize 30 sub-studies comprising 27 888 fully independent subjects. All subjects provided written, informed consent to protocols approved by their institutional ethics boards in accordance with the Helsinki Declaration.</p></sec><sec><title>General cognitive function phenotype</title><p>We examined general cognitive function (‘<italic>g</italic>'), a statistically derived broadband index of within-person performance on a neuropsychological test battery. The <italic>g</italic> phenotype estimates overall performance and is relatively invariant to the battery used and specific cognitive abilities assessed.<sup><xref ref-type="bibr" rid="bib33">33</xref>, <xref ref-type="bibr" rid="bib34">34</xref></sup> As in our prior reports,<sup><xref ref-type="bibr" rid="bib5">5</xref>, <xref ref-type="bibr" rid="bib10">10</xref></sup> for each cohort, <italic>g</italic> was determined using the first unrotated component extracted from a principal components analysis of individual test scores. Details on phenotypic assessments are provided in the supplement. Briefly, each COGENT sub-study (<italic>n</italic>=35) administered an average of 8 (s.d.±4) neuropsychological tests. To be included as a participant in COGENT, data from at least one neuropsychological measure across at least three domains of cognitive performance (for example, digit span for working memory; logical memory for verbal declarative memory; and digit symbol coding for processing speed), or the use of a validated <italic>g</italic>-sensitive measure was required. Digit symbol coding, digit span, verbal memory for words, visual memory, word reading, semantic fluency, verbal memory for stories, vocabulary, phonemic fluency and the trail-making test were the most common tests administered across cohorts. All individual test scores were adjusted (using multiple regression) for age<sup><xref ref-type="bibr" rid="bib2">2</xref></sup> and sex, as well as age × sex and age<sup>2</sup> × sex interaction terms. The average internal consistency across test batteries was 71% (s.d.±12%), and the first unrotated principal component accounted for 42% (s.d.±11%) of the variance in overall test performance, which was expected based on an extensive prior literature (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table S1</xref>).<sup><xref ref-type="bibr" rid="bib35">35</xref></sup></p></sec><sec><title>Genotyping and imputation</title><p>All COGENT samples were genotyped on commercial Illumina or Affymetrix arrays, and a standardized GWAS quality control pipeline was developed and applied to the genetic data as described in detail in the <xref ref-type="supplementary-material" rid="sup1">Supplementary Information</xref>. Participants were of European ancestry, which was confirmed by analysis of genotype data using multidimensional scaling. Genetic clustering in each study was based on multidimensional scaling axis plotting versus four 1000 Genomes Project super populations (African, Admixed American, European and Asian), and non-European participants were removed. Genome-wide imputation was conducted using the largest available cosmopolitan reference cohort.<sup><xref ref-type="bibr" rid="bib36">36</xref></sup></p></sec><sec><title>GWAS meta-analysis</title><p>In each COGENT sample, allelic association analysis of general cognitive function was conducted using imputed allele dosages and the first 10 principal components from the genotyped data to additionally adjust for population stratification. Cohorts of unrelated individuals (27 sub-cohorts) were analyzed using Plink 1.9.<sup><xref ref-type="bibr" rid="bib37">37</xref></sup> Samples including related individuals (8 sub-cohorts) were analyzed with BOLT-LMM<sup><xref ref-type="bibr" rid="bib38">38</xref></sup> using a mixed linear model association function that corrects for population stratification and relatedness.<sup><xref ref-type="bibr" rid="bib39">39</xref></sup> GWAS results were combined for meta-analysis of all 35 sub-studies using the inverse variance-weighted <italic>Z</italic>-score method in METAL.<sup><xref ref-type="bibr" rid="bib40">40</xref></sup> SNPs were filtered according to the following quality control thresholds: (1) minimum imputation quality INFO score of 0.60; (2) minor allele frequency at least 1% and (3) minimum 10 000 samples successfully imputed. Application of these filters resulted in a total of 8 037 763 high-quality SNPs available for meta-analysis in up to 35 298 samples. The standard threshold for genome-wide significance (<italic>P</italic><5 × 10<sup>−8</sup>) was applied to SNP results of the GWAS meta-analysis.</p></sec><sec><title>Gene-based analysis</title><p>Individual SNP results from the meta-analysis were aggregated to conduct a gene-based analysis using MAGMA.<sup><xref ref-type="bibr" rid="bib41">41</xref></sup> SNPs were mapped to genes based on NCBI build 37.3 and defined by the start and stop site ±5 kb, resulting in 18 164 autosomal genes. A genome-wide significance threshold for gene-based associations was calculated using the Bonferroni method (<italic>α</italic>=0.05/18 164; <italic>P</italic>=2.75 × 10<sup>−6</sup>).</p></sec><sec><title>Genetic correlation analysis</title><p>LD score regression<sup><xref ref-type="bibr" rid="bib28">28</xref>, <xref ref-type="bibr" rid="bib29">29</xref></sup> was used to derive genetic correlations among GWAS results for general cognitive function and publicly available GWAS results from multiple neurobehavioral phenotypes of potential relevance. LD score regression quantifies the extent to which two phenotypes share genetic etiology (at least with respect to common variation captured by GWAS). GWAS summary statistics for 29 phenotypes were downloaded and processed similar to the pipeline of Bulik-Sullivan <italic>et al.</italic><sup><xref ref-type="bibr" rid="bib29">29</xref></sup> The following phenotypes were included—cognition: childhood intelligence, educational attainment and obtaining a college degree; neurodevelopmental: autism and attention-deficit/hyperactivity disorder; neuropsychiatric: schizophrenia, bipolar disorder, anxiety and major depression; tobacco use: ever smoked cigarettes, number of cigarettes per day, age of onset of smoking and being a former smoker; personality: neuroticism, extraversion, openness, agreeableness and conscientiousness; brain volume: intracranial volume, nucleus accumbens, caudate nucleus, putamen, globus pallidus, hippocampus and thalamus; early childhood growth and development: infant head circumference, birth length and birth weight. URLs and references for data sources are provided in the <xref ref-type="supplementary-material" rid="sup1">Supplementary Information</xref>.</p></sec></sec><sec><title>Results</title><sec><title>GWAS of general cognitive function</title><p>The QQ plot (<xref ref-type="supplementary-material" rid="sup1">Supplementary Figure 1</xref>) demonstrates <italic>λ</italic><sub>GC</sub> was 1.12, comparable to the value (1.14) observed in the recent CHARGE meta-analysis of cognitive ability.<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> The LD score regression intercept of 1.04 indicates that polygenicity, rather than residual population stratification, accounted for most of the increase in the mean <italic>χ</italic><sup>2</sup> statistic.<sup><xref ref-type="bibr" rid="bib28">28</xref>, <xref ref-type="bibr" rid="bib29">29</xref></sup> As shown in the Manhattan plot (<xref ref-type="fig" rid="fig1">Figure 1</xref>), two loci surpassed the genome-wide threshold of <italic>P</italic>⩽5 × 10<sup>−8</sup> in our GWAS meta-analysis (see <xref ref-type="supplementary-material" rid="sup1">Supplementary Table S2</xref> for more details). On chromosome 2 (<xref ref-type="fig" rid="fig2">Figure 2</xref>, top), intronic SNP rs76114856 in the centromere protein O (<italic>CENPO)</italic> gene was genome-wide significant (<italic>P</italic>=6.58 × 10<sup>−9</sup>). On chromosome 1 (<xref ref-type="fig" rid="fig2">Figure 2</xref>, bottom), a cluster of six SNPs located in a lincRNA, RP4-665J23.1 (also known as <italic>LOC105378853</italic>), were also genome-wide significant (top SNP, rs6669072, <italic>P</italic>=2.77 × 10<sup>−8</sup>). Values of meta-analytic tests of heterogeneity were low and not statistically significant, indicating that outlier cohorts did not drive significant results. In addition, a large 1.4 Mb region at chromosome 17q21.31, coextensive with a known inversion polymorphism,<sup><xref ref-type="bibr" rid="bib42">42</xref></sup> harbored 101 nearly significant SNPs (all <italic>P</italic>'s<10<sup>−6</sup>; top SNP, rs916888, <italic>P</italic>=8.18 × 10<sup>−8</sup>).</p></sec><sec><title>Gene-based analysis of general cognitive function</title><p>Seven genes in three chromosomal regions (<italic>WNT3</italic>, <italic>PLEKHM1</italic> and <italic>ARHGAP27</italic> at chromosome 17q21.31; <italic>TP53</italic> and <italic>WRAP53</italic> at chromosome 17p13.1; and <italic>ATXN7L2</italic> and <italic>CYB561D1</italic> at chromosome 1p13.3) were significantly associated with cognitive function after Bonferroni correction (<xref rid="tbl2" ref-type="table">Table 2</xref>). Several genes at these loci, including <italic>NSF</italic>, <italic>STH</italic>, <italic>KANSL1</italic>, <italic>CRHR1</italic> and <italic>MAPT</italic> in the 17q21.31 inversion region, demonstrate association just below the Bonferroni-corrected threshold.</p></sec><sec><title>SNP lookups from published GWAS of cognition and educational attainment</title><p>We sought to expand the utility of our data by using it as a lookup table to confirm and extend associations previously reported in large-scale GWAS of cognition (from the CHARGE consortium<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> and the UK Biobank<sup><xref ref-type="bibr" rid="bib8">8</xref></sup>) and educational attainment (from the SSGAC consortium<sup><xref ref-type="bibr" rid="bib9">9</xref></sup>). First, we looked up all cognitive SNPs nominally associated in the CHARGE study at <italic>P</italic><10<sup>−5</sup>. Importantly, because of partial sample overlap between COGENT and CHARGE, we re-ran our cognitive GWAS excluding five overlapping cohorts (CHS, FHS, HBCS, LBC1936 and NCNG). A meta-analytic <italic>P</italic>-value was then generated across the two studies for those loci with nominal <italic>P</italic><0.05 in COGENT. As shown in <xref ref-type="supplementary-material" rid="sup1">Supplementary Table S3</xref>, we found support for the three genome-wide significant loci reported in CHARGE, as well as support for an additional, novel locus at chromosome 3p22.3 that attained a meta-analytic <italic>P</italic>-value surpassing the genome-wide significance threshold (rs1523041, <italic>P</italic>=5.46 × 10<sup>−10</sup>). This SNP is intergenic; however, publicly available gene expression data (from GTEx<sup><xref ref-type="bibr" rid="bib43">43</xref></sup>) have shown that rs1523041 is an expression quantitative trait locus for the <italic>ARPP21</italic> gene (<xref ref-type="supplementary-material" rid="sup1">Supplementary Figure 1</xref>).</p><p>Next, we examined the genome-wide significant SNPs reported from the UK Biobank study of verbal numerical reasoning and reaction time to determine if these were also associated with general cognitive ability. As shown in <xref ref-type="supplementary-material" rid="sup1">Supplementary Table S4</xref>, we found nominally significant support for the chromosome 22 locus associated with verbal numerical reasoning (top local SNP in COGENT, rs12170228, <italic>P</italic>=0.0053, same direction of effect in COGENT and UK Biobank). We also showed a similar trend for the chromosome 7 locus associated with verbal numerical reasoning (rs9771228, <italic>P</italic>=0.074 in COGENT, same direction of effect in COGENT and UK Biobank). The lone SNP on chromosome 14 that attained genome-wide significance in the UK Biobank GWAS of verbal numerical reasoning was a rare variant (MAF=0.1%) that was not available in COGENT and has no known proxies. For the two loci reported to be associated with reaction time in UK Biobank, COGENT results demonstrated the same direction of allelic effects, but were not statistically significant (COGENT <italic>P</italic>'s>0.6).</p><p>Finally, we looked up all SNPs that represented independent, genome-wide significant hits for educational attainment from the combined SSGAC+UK Biobank cohorts. Of a total of 164 SNPs meeting this criteria (as listed in Table 1.16 of that report<sup><xref ref-type="bibr" rid="bib9">9</xref></sup>), 143 SNPs were directly available in COGENT, and an additional 12 SNPs were tested by proxy (9 SNPs were unavailable in COGENT even by proxy). There were 31 educational attainment SNPs that were nominally significant at <italic>P</italic><0.05 in COGENT, all in the same direction of effect as for educational attainment, representing a highly significant enrichment (<italic>P</italic>=3.9 × 10<sup>−11</sup>, binomial test) of overlap between years of education and cognitive function (<xref ref-type="supplementary-material" rid="sup1">Supplementary Table S5</xref>). Further, two SNPs (rs7593947 and rs2568955) were Bonferroni-corrected significant (for 155 tests; <italic>P</italic><3.23 × 10<sup>−4</sup>), suggesting two specific loci for cognition were discovered using this ‘proxy-phenotype' method.<sup><xref ref-type="bibr" rid="bib11">11</xref></sup> Notably, GTEx data reveal that rs2568955 is a strongly significant expression quantitative trait locus (<xref ref-type="supplementary-material" rid="sup1">Supplementary Figure 2</xref>) in brain tissue for <italic>RPL31P12</italic>, although this gene is annotated as a pseudogene; rs7593947 is an intronic variant in the <italic>BCL11A</italic> gene.</p></sec><sec><title>Genetic correlation of general cognitive function with related complex traits</title><p>SNP heritability (due to common variation) as calculated using LD score regression was 21.5% (s.e.=0.01%). This value for <italic>h</italic><sup>2</sup><sub>g</sub> is slightly lower than prior studies<sup><xref ref-type="bibr" rid="bib7">7</xref>, <xref ref-type="bibr" rid="bib8">8</xref></sup> which utilized the GCTA approach in single samples; this attenuation is expected based on the fact that LD score regression utilizes summary scores as opposed to full SNP data. The results of the LD score regression-based genetic correlations with other neurobehavioral phenotypes are detailed in <xref rid="tbl3" ref-type="table">Table 3</xref>. Note that our use of the LD score regression approach applied a stringent correction (unconstrained intercept) for potential sample overlap and population stratification, as well as a conservative Bonferroni correction for multiple phenotypes. Not surprisingly, strongly significant positive correlations were observed with the most closely related phenotypes: years of education (<italic>P</italic>=1.48 × 10<sup>−63</sup>), obtaining a college degree (<italic>P</italic>=1.88 × 10<sup>−23</sup>) and childhood intelligence (<italic>P</italic>=1.24 × 10<sup>−13</sup>). A significant negative correlation was observed with schizophrenia (<italic>P</italic>=4.09 × 10<sup>−4</sup>), such that genetic load for lower cognitive scores was associated with greater risk for schizophrenia, consistent with prior reports from COGENT<sup><xref ref-type="bibr" rid="bib5">5</xref></sup> and others.<sup><xref ref-type="bibr" rid="bib28">28</xref>, <xref ref-type="bibr" rid="bib30">30</xref></sup> Similar trends were observed for attention-deficit/hyperactivity disorder and anxiety, with nominal (but not Bonferroni-corrected) levels of statistical significance. A Bonferroni-corrected significant positive correlation was observed for autism (<italic>P</italic>=6.00 × 10<sup>−4</sup>), again consistent with prior reports.<sup><xref ref-type="bibr" rid="bib30">30</xref>, <xref ref-type="bibr" rid="bib44">44</xref></sup></p><p>A novel observation is a significant, positive genetic correlation between general cognitive ability and the personality trait of openness (<italic>r</italic><sub>g</sub>=0.48; <italic>P</italic>=3.25 × 10<sup>−4</sup>); no other correlations with personality traits were even nominally significant. (It should be noted that agreeableness was the only trait for which the SNP-based heritability did not significantly differ from zero (<italic>h</italic><sup>2</sup><sub>g</sub>=0.016; s.e.=0.029) and was, therefore, not included in correlational analyses). Higher cognitive ability was strongly genetically correlated with reduced rates of smoking (<italic>P</italic>=2.13 × 10<sup>−4</sup>) and greater rates of quitting smoking (<italic>P</italic>=5.09 × 10<sup>−3</sup>).</p><p>Nominally significant positive genetic correlations were observed with birth length and weight, with similar trends for infant head circumference. All genetic correlations with neuroanatomic measures trended in the positive direction (larger brain volumes associated with higher cognitive ability), consistent with a large literature revealing correlations at the phenotypic level,<sup><xref ref-type="bibr" rid="bib45">45</xref></sup> although none of the genetic correlations attained nominal significance under our conservative approach.</p></sec></sec><sec><title>Discussion</title><p>Our GWAS meta-analysis of general cognitive function in a sample of 35 298 individuals of European ancestry revealed two novel associated SNP loci, three novel gene-based loci, and provided added support for several previously reported associations. Strengths of our study included access to individual-level genetic and neuropsychological data, which allowed us to run each sample through uniform genotype and phenotype quality control pipelines. Specifically, the general cognitive function phenotype was well characterized as a composite score derived from relatively large batteries of both verbal and nonverbal neuropsychological tests. Genotype data were processed with the latest imputation platforms and analytic procedures.</p><p>Our top GWAS hit was rs76114856, of which the minor T allele was associated with reduced cognitive performance. This SNP is an intronic variant in the <italic>CENPO</italic> gene, which encodes a component of the interphase centromere complex.<sup><xref ref-type="bibr" rid="bib46">46</xref></sup> This gene is highly expressed in the basal ganglia and thalamus of the human brain.<sup><xref ref-type="bibr" rid="bib65">65</xref></sup><italic>CENPO</italic> is located at chromosome 2p23.3 and has prior GWAS associations to height.<sup><xref ref-type="bibr" rid="bib1">1</xref>, <xref ref-type="bibr" rid="bib47">47</xref></sup> The <italic>CENPO</italic> gene also had a nominal association to cognition in our gene-based analysis at <italic>P</italic><0.05, as did neighboring genes <italic>NCOA1</italic>, <italic>PTRHD1</italic> and <italic>ADCY3</italic>. The second strongest GWAS signal fell within a large intergenic non-coding RNA (lincRNA) of unknown function, RP4-665J23.1. Neighboring protein-coding genes are poorly annotated and do not provide strong clues as to the potential biological mechanism underlying the association.</p><p>We also found evidence that the chromosome 17q21.31 inversion region is associated with cognitive function. The chromosome 17q21.31 inversion consists of two haplotypes (H1 and H2), and the absence of recombination across the ~1.5 Mb region between the inverted (H2) and the noninverted (H1) chromosomes has resulted in two families of chromosomes.<sup><xref ref-type="bibr" rid="bib48">48</xref></sup> H1 chromosomes comprise the common (~80% frequency in European samples) noninverted gene order, whereas the H2 haplotype comprises the inverted gene order (~20% in European samples).<sup><xref ref-type="bibr" rid="bib48">48</xref></sup> There are several sources of evidence that variation at this locus is associated with neurobehavioral phenotypes. For example, the 17q21.31 microdeletion syndrome is associated with the H2 haplotype, which carries additional low-copy repeats susceptible to non-allelic homologous recombination. The syndrome is characterized clinically by developmental delay/intellectual disability, neonatal/childhood hypotonia, friendly behavior and specific facial dysmorphisms.<sup><xref ref-type="bibr" rid="bib49">49</xref></sup> Notably, <italic>KANSL1</italic> gene disruption is associated with the full clinical spectrum of 17q21.31 microdeletion syndrome.<sup><xref ref-type="bibr" rid="bib49">49</xref></sup> In addition, the region harbors the <italic>MAPT</italic> gene, encoding microtubule-associated protein tau, a hallmark of multiple dementias.<sup><xref ref-type="bibr" rid="bib48">48</xref>, <xref ref-type="bibr" rid="bib50">50</xref>, <xref ref-type="bibr" rid="bib51">51</xref>, <xref ref-type="bibr" rid="bib52">52</xref></sup> The H1 family of haplotypes has been associated with increased risk for late-life tauopathies, diseases marked by the accumulation of MAPT neurofibrillary tangles in nerve cells, such as sporadic frontotemporal dementia,<sup><xref ref-type="bibr" rid="bib53">53</xref></sup> Alzheimer's disease,<sup><xref ref-type="bibr" rid="bib54">54</xref></sup> Parkinson's disease<sup><xref ref-type="bibr" rid="bib55">55</xref></sup> and progressive supranuclear palsy.<sup><xref ref-type="bibr" rid="bib48">48</xref></sup> By contrast, the H2 haplotype has been associated with developmental delay and learning difficulties,<sup><xref ref-type="bibr" rid="bib51">51</xref>, <xref ref-type="bibr" rid="bib56">56</xref>, <xref ref-type="bibr" rid="bib57">57</xref>, <xref ref-type="bibr" rid="bib58">58</xref></sup> as well as reduced intracranial volume.<sup><xref ref-type="bibr" rid="bib52">52</xref></sup> Consistent with these latter observations, our data suggest alleles corresponding to the H2 haplotype are associated with worse cognitive performance.</p><p>In addition to the loci attaining clear genome-wide significance through our primary SNP-based and gene-based analyses, our results confirmed and extended prior GWAS studies of cognitive and educational phenotypes. Although a prior COGENT report provided converging evidence for a role of a chromosome 6 locus (rs1906252),<sup><xref ref-type="bibr" rid="bib10">10</xref></sup> we now provide further support for the <italic>NPAS3</italic>/<italic>AKAP6</italic> locus on chromosome 14 previously reported by the CHARGE consortium. <italic>NPAS3</italic> is a promising candidate gene, as it has a role in neurodevelopment, and disruptions of this gene have been associated with psychiatric and intellectual disability phenotypes.<sup><xref ref-type="bibr" rid="bib59">59</xref>, <xref ref-type="bibr" rid="bib60">60</xref></sup></p><p>In the context of prior associations to cognitive and educational phenotypes, our data identified several loci with strong empirical support for a role in cognition. Of these, two are noteworthy for representing known expression quantitative trait locus, permitting inference of potential biological mechanisms underlying the statistical associations. Specifically, we found that the major (C) allele at rs1523041 was strongly (<italic>P</italic>=5.46 × 10<sup>−10</sup>) associated with better cognitive performance; this allele drives lower expression of the <italic>ARPP21</italic> gene (<xref ref-type="supplementary-material" rid="sup1">Supplementary Figure S1</xref>). <italic>ARPP21</italic> encodes a cAMP-regulated phosphoprotein, enriched in the basal ganglia and cerebellum, that has a central role in the integration of neurotransmitter inputs into striatal medium spiny neurons.<sup><xref ref-type="bibr" rid="bib61">61</xref></sup> Intriguingly, a deletion encompassing this gene segregated with syndromic intellectual disability in a multiply affected pedigree.<sup><xref ref-type="bibr" rid="bib62">62</xref></sup> Similarly, we found that the minor (T) allele of rs2568955 was associated with poorer cognitive performance, and this allele is associated with greater expression of <italic>RPL31P12</italic> (<xref ref-type="supplementary-material" rid="sup1">Supplementary Figure S2</xref>). It should be noted that the strongest expression quantitative trait locus associations for these SNPs were observed in non-brain tissue in the GTEx database, perhaps due to smaller sample sizes available for neuronal phenotypes; these results should be tested in larger studies of brain expression that will soon be forthcoming. <italic>BCL11A</italic> is also a promising candidate gene for cognition. Haploinsufficiency of this gene has been associated with intellectual disability in a large clinical study, with the phenotype recapitulated in <italic>Bcl11a</italic> knockout mice, which was shown to be mediated through downstream transcriptional dysregulation in the hippocampus and cortex.<sup><xref ref-type="bibr" rid="bib63">63</xref></sup></p><p>Analysis of the genetic correlation between general cognitive function and various other phenotypes revealed that better cognitive performance was robustly genetically correlated with more years of schooling, decreased likelihood of smoking and decreased risk for several psychiatric disorders (as well as increased risk for autism). These results are generally consistent with recent genetic correlation studies of cognitive phenotypes<sup><xref ref-type="bibr" rid="bib30">30</xref></sup> and proxy phenotypes for cognition.<sup><xref ref-type="bibr" rid="bib9">9</xref></sup> The personality trait of openness, a core component of the ‘Big 5' model of personality, was positively correlated with cognitive ability at the genetic level. This novel finding is consistent with a prior literature in which moderate phenotypic correlations (values for <italic>r</italic> ranging between 0.25 and 0.5) between openness and cognitive ability have been repeatedly observed,<sup><xref ref-type="bibr" rid="bib20">20</xref>, <xref ref-type="bibr" rid="bib64">64</xref></sup> whereas cognition is generally uncorrelated with other personality dimensions. Moreover, phenotypic data from twin and family studies have suggested a specific genetic correlation between openness and general cognitive ability.<sup><xref ref-type="bibr" rid="bib65">65</xref></sup> Longitudinal studies have suggested a model in which openness may serve as a ‘buffer' against cognitive decline, as has been proposed in the Openness-Fluid-Crystallized-Intelligence model applied to late adulthood.<sup><xref ref-type="bibr" rid="bib66">66</xref></sup> Positive genetic correlations with birth length and weight suggest a critical role for prenatal developmental factors in the subsequent manifestation of cognitive ability throughout the lifespan.</p><p>One limitation of the current study is the wide age range of subjects, both across cohorts and within cohorts. Although we sought to control for confounding effects of age using covariates, genetic influence on cognitive ability is somewhat reduced in early childhood and adolescence relative to adulthood.<sup><xref ref-type="bibr" rid="bib67">67</xref></sup> In addition, late-life effects of cognitive decline may be mediated through somewhat disparate molecular pathways; this may explain the relatively weak effect of variation at <italic>APOE</italic> compared with prior GWAS meta-analysis.<sup><xref ref-type="bibr" rid="bib7">7</xref></sup> Nevertheless, cognitive abilities are remarkably stable across the entire lifespan,<sup><xref ref-type="bibr" rid="bib68">68</xref></sup> so we chose to include all available samples in order to maximize sample size and power.</p><p>Similarly, we chose to include cohorts with widely disparate neurocognitive batteries, which undoubtedly contributed to noise surrounding the estimates of <italic>g.</italic> Moreover, as demonstrated in <xref ref-type="supplementary-material" rid="sup1">Supplementary Table 1</xref>, the degree to which the first principal component captured the shared variance across tests was heterogeneous across cohorts. In general, cohorts with fewer available tests demonstrated greater loading onto the first factor, but with less reliability as determined by Cronbach's <italic>α</italic>. However, in each case, the scree plots clearly demonstrated a steep drop in variance accounted for beyond the first component, consistent with the known properties of <italic>g.</italic> Moreover, in a subset of subjects in one of the cohorts (TOP), we previously<sup><xref ref-type="bibr" rid="bib5">5</xref></sup> compared our computed <italic>g</italic> with estimated intelligence quotient from a 4-subscale composite from the WASI,<sup><xref ref-type="bibr" rid="bib69">69</xref></sup> and observed a strong correlation (<italic>r</italic>=0.67, <italic>P</italic><10<sup>−46</sup>). Thus, we are confident that our computed index for each cohort was primarily reflecting general cognitive ability, but it is equally certain that substantial heterogeneity existed across cohorts, thereby reducing power in comparison with more easily measured quantitative traits such as height. Notably, it has been empirically demonstrated that such noise is more than compensated by increases in statistical power.<sup><xref ref-type="bibr" rid="bib70">70</xref></sup> Given the expense in conducting comprehensive cognitive assessments, we chose to include all available cohorts meeting our basic criteria.</p><p>Despite the statistical significance of the novel GWAS loci identified in the current report, it is important to emphasize that the effect sizes for individual SNPs are very small; each of our top two SNPs individually account for ~0.1% of the variance in cognitive performance. For context, these effect sizes are considerably smaller than those observed for the top individual loci associated with other quantitative anthropometric traits such as height and weight,<sup><xref ref-type="bibr" rid="bib1">1</xref>, <xref ref-type="bibr" rid="bib2">2</xref></sup> This difference may reflect the complexity of the underlying genetic architecture of cognition, as >80% of all genes are expressed in brain;<sup><xref ref-type="bibr" rid="bib71">71</xref></sup> this complexity has also slowed progress in identifying genetic loci for neuropsychiatric disorders, given the potentially large mutational target.<sup><xref ref-type="bibr" rid="bib70">70</xref></sup> This challenge is exacerbated by the fact that general cognitive ability is a latent trait that is only indirectly captured by the available phenotypic measures, which are also quite heterogeneous across cohorts. Moreover, the well-known winners' curse phenomenon<sup><xref ref-type="bibr" rid="bib72">72</xref></sup> will likely result in even further reduction of our effect size estimates in future studies of independent cohorts. However, as described in the preceding paragraphs, results of the present study can provide important information about the molecular underpinnings of cognitive function as well as clues relevant to the etiology neuropsychiatric disorders and other conditions relevant to human health. Although it is striking that general cognitive ability remains the quantitative trait most challenging to GWAS methodology, the recent success of very large-scale GWAS in educational attainment<sup><xref ref-type="bibr" rid="bib9">9</xref></sup> provides optimism that cognition is now at the beginning of the slope of increasing GWAS discovery that has been observed for all heritable complex traits.<sup><xref ref-type="bibr" rid="bib73">73</xref></sup></p></sec></body><back><ack><p>This work has been supported by grants from the National Institutes of Health (R01MH079800 and P50 MH080173 to AKM; R01 MH080912 to DCG; K23 MH077807 to KEB; K01 MH085812 to MCK). Data collection for the TOP cohort was supported by the Research Council of Norway, South-East Norway Health Authority and KG Jebsen Foundation. The NCNG study was supported by Research Council of Norway Grants 154313/V50 and 177458/V50. The NCNG GWAS was financed by grants from the Bergen Research Foundation, the University of Bergen, the Research Council of Norway (FUGE, Psykisk Helse), Helse Vest RHF and Dr Einar Martens Fund. The Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. For the LBC1936 cohort, phenotype collection was supported by The Disconnected Mind project. Genotyping was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC grant no. BB/F019394/1). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative, which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). The CAMH work was supported by the CAMH Foundation and the Canadian Institutes of Health Research. The Duke Cognition Cohort (DCC) acknowledges K Linney, JM McEvoy, P Hunt, V Dixon, T Pennuto, K Cornett, D Swilling, L Phillips, M Silver, J Covington, N Walley, J Dawson, H Onabanjo, P Nicoletti, A Wagoner, J Elmore, L Bevan, J Hunkin and R Wilson for recruitment and testing of subjects. DCC also acknowledges the Ellison Medical Foundation New Scholar award AG-NS-0441-08 for partial funding of this study as well as the National Institute of Mental Health of the National Institutes of Health under award number K01MH098126. The UCLA Consortium for Neuropsychiatric Phenomics (CNP) study acknowledges the following sources of funding from the NIH: Grants UL1DE019580 and PL1MH083271 (RMB), RL1MH083269 (TDC), RL1DA024853 (EL) and PL1NS062410. The ASPIS study was supported by National Institute of Mental Health research grants R01MH085018 and R01MH092515 to Dr Dimitrios Avramopoulos. Support for the Duke Neurogenetics Study was provided the National Institutes of Health (R01 DA033369 and R01 AG049789 to ARH) and by a National Science Foundation Graduate Research Fellowship to MAS. Recruitment, genotyping and analysis of the TCD healthy control samples were supported by Science Foundation Ireland (grants 12/IP/1670, 12/IP/1359 and 08/IN.1/B1916).</p></ack><fn-group><fn><p><xref ref-type="supplementary-material" rid="sup1">Supplementary Information</xref> accompanies the paper on the <italic>Molecular Psychiatry</italic> website (http://www.nature.com/mp)</p></fn><fn fn-type="COI-statement"><p>The authors declare no conflict of interest.</p></fn></fn-group><ref-list><ref id="bib1"><mixed-citation publication-type="journal">Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S et al. <article-title>Defining the role of common variation in the genomic and biological architecture of adult human height</article-title>. <source>Nat Genet</source><year>2014</year>; <volume>46</volume>: <fpage>1173</fpage>–1186.<pub-id pub-id-type="pmid">25282103</pub-id></mixed-citation></ref><ref id="bib2"><mixed-citation publication-type="journal">Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR et al. <article-title>Genetic studies of body mass index yield new insights for obesity biology</article-title>. <source>Nature</source><year>2015</year>; 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Green arrows indicate loci attaining genome-wide significance (red line, <italic>P</italic><5 × 10<sup>−8</sup>). Gray arrow indicates locus at chromosome 17q21.31 approaching genome-wide significance.</p></caption><graphic xlink:href="mp2016244f1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Region plots depicting genome-wide significant loci on Chromosome 2 (top) and Chromosome 1 (bottom). Local linkage disequilibrium (<italic>r</italic><sup>2</sup>) is color-coded as shown in the legend, and local recombination rate is depicted by the bright blue peaks (magnitude indicated by the right-hand <italic>y</italic> axis).</p></caption><graphic xlink:href="mp2016244f2"></graphic></fig><table-wrap id="tbl1"><label>Table 1</label><caption><title>Demographic characteristics of the consortium</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Cohort</italic></th><th align="left" valign="top" charoff="50"><italic>Study name</italic></th><th align="left" valign="top" charoff="50"><italic>Country</italic></th><th align="center" valign="top" char="." charoff="50">N</th><th align="center" valign="top" char="." charoff="50"><italic>Age mean</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Age s.d.</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Min age</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Max age</italic></th><th align="center" valign="top" char="." charoff="50">N <italic>Male</italic></th><th align="center" valign="top" char="." charoff="50"><italic>% Male</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">ACPRC</td><td align="left" valign="top" charoff="50">Age and Cognitive Performance Research Cohort</td><td align="left" valign="top" charoff="50">UK</td><td align="char" valign="top" char="." charoff="50">1461</td><td align="char" valign="top" char="." charoff="50">64.7</td><td align="char" valign="top" char="." charoff="50">6.1</td><td align="char" valign="top" char="." charoff="50">47</td><td align="char" valign="top" char="." charoff="50">85</td><td align="char" valign="top" char="." charoff="50">425</td><td align="char" valign="top" char="." charoff="50">0.29</td></tr><tr><td align="left" valign="top" charoff="50">ADNI</td><td align="left" valign="top" charoff="50">Alzheimer's Disease Neuroimaging Initiative</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">259</td><td align="char" valign="top" char="." charoff="50">75.3</td><td align="char" valign="top" char="." charoff="50">5.1</td><td align="char" valign="top" char="." charoff="50">62</td><td align="char" valign="top" char="." charoff="50">90</td><td align="char" valign="top" char="." charoff="50">137</td><td align="char" valign="top" char="." charoff="50">0.53</td></tr><tr><td align="left" valign="top" charoff="50">ASPIS</td><td align="left" valign="top" charoff="50">Athens Study of Psychosis Proneness and Incidence of Schizophrenia</td><td align="left" valign="top" charoff="50">Greece</td><td align="char" valign="top" char="." charoff="50">919</td><td align="char" valign="top" char="." charoff="50">20.7</td><td align="char" valign="top" char="." charoff="50">1.9</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">919</td><td align="char" valign="top" char="." charoff="50">1.00</td></tr><tr><td align="left" valign="top" charoff="50">CAMH</td><td align="left" valign="top" charoff="50">Center for Addiction and Mental Health</td><td align="left" valign="top" charoff="50">Canada</td><td align="char" valign="top" char="." charoff="50">80</td><td align="char" valign="top" char="." charoff="50">48.6</td><td align="char" valign="top" char="." charoff="50">19.4</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">86</td><td align="char" valign="top" char="." charoff="50">38</td><td align="char" valign="top" char="." charoff="50">0.48</td></tr><tr><td align="left" valign="top" charoff="50">CHS</td><td align="left" valign="top" charoff="50">Cardiovascular Health Study</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">2931</td><td align="char" valign="top" char="." charoff="50">77.3</td><td align="char" valign="top" char="." charoff="50">5.3</td><td align="char" valign="top" char="." charoff="50">69</td><td align="char" valign="top" char="." charoff="50">96</td><td align="char" valign="top" char="." charoff="50">1208</td><td align="char" valign="top" char="." charoff="50">0.41</td></tr><tr><td align="left" valign="top" charoff="50">CNP</td><td align="left" valign="top" charoff="50">UCLA Consortium for Neuropsychiatric Phenomics</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">628</td><td align="char" valign="top" char="." charoff="50">31.1</td><td align="char" valign="top" char="." charoff="50">8.3</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">50</td><td align="char" valign="top" char="." charoff="50">310</td><td align="char" valign="top" char="." charoff="50">0.49</td></tr><tr><td align="left" valign="top" charoff="50">DCC</td><td align="left" valign="top" charoff="50">Duke Cognition Cohort</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">1193</td><td align="char" valign="top" char="." charoff="50">27.1</td><td align="char" valign="top" char="." charoff="50">11.6</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">77</td><td align="char" valign="top" char="." charoff="50">558</td><td align="char" valign="top" char="." charoff="50">0.47</td></tr><tr><td align="left" valign="top" charoff="50">DNS</td><td align="left" valign="top" charoff="50">Duke Neurogenetics Study</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">455</td><td align="char" valign="top" char="." charoff="50">19.8</td><td align="char" valign="top" char="." charoff="50">1.3</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">22</td><td align="char" valign="top" char="." charoff="50">212</td><td align="char" valign="top" char="." charoff="50">0.47</td></tr><tr><td align="left" valign="top" charoff="50">DUBLIN</td><td align="left" valign="top" charoff="50">Galway and Dublin, Ireland</td><td align="left" valign="top" charoff="50">Ireland</td><td align="char" valign="top" char="." charoff="50">135</td><td align="char" valign="top" char="." charoff="50">36.2</td><td align="char" valign="top" char="." charoff="50">12.5</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">60</td><td align="char" valign="top" char="." charoff="50">71</td><td align="char" valign="top" char="." charoff="50">0.53</td></tr><tr><td align="left" valign="top" charoff="50">FHS</td><td align="left" valign="top" charoff="50">Framingham Heart Study</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">5360</td><td align="char" valign="top" char="." charoff="50">51.7</td><td align="char" valign="top" char="." charoff="50">10.8</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">87</td><td align="char" valign="top" char="." charoff="50">2460</td><td align="char" valign="top" char="." charoff="50">0.46</td></tr><tr><td align="left" valign="top" charoff="50">GCAP</td><td align="left" valign="top" charoff="50">NIMH Genes, Cognition and Psychosis Program</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">964</td><td align="char" valign="top" char="." charoff="50">33.8</td><td align="char" valign="top" char="." charoff="50">9.8</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">61</td><td align="char" valign="top" char="." charoff="50">438</td><td align="char" valign="top" char="." charoff="50">0.45</td></tr><tr><td align="left" valign="top" charoff="50">GENADA</td><td align="left" valign="top" charoff="50">Genotype–Phenotype Associations in Alzheimer's Disease</td><td align="left" valign="top" charoff="50">Canada</td><td align="char" valign="top" char="." charoff="50">767</td><td align="char" valign="top" char="." charoff="50">73.4</td><td align="char" valign="top" char="." charoff="50">7.9</td><td align="char" valign="top" char="." charoff="50">48</td><td align="char" valign="top" char="." charoff="50">94</td><td align="char" valign="top" char="." charoff="50">279</td><td align="char" valign="top" char="." charoff="50">0.36</td></tr><tr><td align="left" valign="top" charoff="50">HBCS</td><td align="left" valign="top" charoff="50">Helsinki Birth Cohort Study</td><td align="left" valign="top" charoff="50">Finland</td><td align="char" valign="top" char="." charoff="50">299</td><td align="char" valign="top" char="." charoff="50">67.7</td><td align="char" valign="top" char="." charoff="50">2.3</td><td align="char" valign="top" char="." charoff="50">64</td><td align="char" valign="top" char="." charoff="50">75</td><td align="char" valign="top" char="." charoff="50">299</td><td align="char" valign="top" char="." charoff="50">1.00</td></tr><tr><td align="left" valign="top" charoff="50">IBG</td><td align="left" valign="top" charoff="50">Institute for Behavioral Genetics</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">260</td><td align="char" valign="top" char="." charoff="50">15.9</td><td align="char" valign="top" char="." charoff="50">1.5</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">19</td><td align="char" valign="top" char="." charoff="50">235</td><td align="char" valign="top" char="." charoff="50">0.90</td></tr><tr><td align="left" valign="top" charoff="50">LBC1936</td><td align="left" valign="top" charoff="50">Lothian Birth Cohort 1936 Study</td><td align="left" valign="top" charoff="50">UK</td><td align="char" valign="top" char="." charoff="50">951</td><td align="char" valign="top" char="." charoff="50">69.6</td><td align="char" valign="top" char="." charoff="50">0.8</td><td align="char" valign="top" char="." charoff="50">68</td><td align="char" valign="top" char="." charoff="50">71</td><td align="char" valign="top" char="." charoff="50">509</td><td align="char" valign="top" char="." charoff="50">0.54</td></tr><tr><td align="left" valign="top" charoff="50">LLFS</td><td align="left" valign="top" charoff="50">Long Life Family Study</td><td align="left" valign="top" charoff="50">USA and Denmark</td><td align="char" valign="top" char="." charoff="50">4081</td><td align="char" valign="top" char="." charoff="50">68.1</td><td align="char" valign="top" char="." charoff="50">14.0</td><td align="char" valign="top" char="." charoff="50">24</td><td align="char" valign="top" char="." charoff="50">90</td><td align="char" valign="top" char="." charoff="50">1861</td><td align="char" valign="top" char="." charoff="50">0.46</td></tr><tr><td align="left" valign="top" charoff="50">LOAD</td><td align="left" valign="top" charoff="50">Late Onset Alzheimer's Disease Family Study</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">1033</td><td align="char" valign="top" char="." charoff="50">75.1</td><td align="char" valign="top" char="." charoff="50">5.7</td><td align="char" valign="top" char="." charoff="50">53</td><td align="char" valign="top" char="." charoff="50">95</td><td align="char" valign="top" char="." charoff="50">379</td><td align="char" valign="top" char="." charoff="50">0.37</td></tr><tr><td align="left" valign="top" charoff="50">LOGOS</td><td align="left" valign="top" charoff="50">Learning on Genetics of Schizophrenia Spectrum</td><td align="left" valign="top" charoff="50">Crete</td><td align="char" valign="top" char="." charoff="50">795</td><td align="char" valign="top" char="." charoff="50">22.5</td><td align="char" valign="top" char="." charoff="50">3.8</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">37</td><td align="char" valign="top" char="." charoff="50">795</td><td align="char" valign="top" char="." charoff="50">1.00</td></tr><tr><td align="left" valign="top" charoff="50">MCTFR</td><td align="left" valign="top" charoff="50">Minnesota Center for Twin and Family Research</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">5448</td><td align="char" valign="top" char="." charoff="50">32.5</td><td align="char" valign="top" char="." charoff="50">14.2</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">65</td><td align="char" valign="top" char="." charoff="50">2349</td><td align="char" valign="top" char="." charoff="50">0.43</td></tr><tr><td align="left" valign="top" charoff="50">MUNICH</td><td align="left" valign="top" charoff="50">Munich, Germany</td><td align="left" valign="top" charoff="50">Germany</td><td align="char" valign="top" char="." charoff="50">1095</td><td align="char" valign="top" char="." charoff="50">47.8</td><td align="char" valign="top" char="." charoff="50">15.3</td><td align="char" valign="top" char="." charoff="50">19</td><td align="char" valign="top" char="." charoff="50">76</td><td align="char" valign="top" char="." charoff="50">540</td><td align="char" valign="top" char="." charoff="50">0.49</td></tr><tr><td align="left" valign="top" charoff="50">NCNG</td><td align="left" valign="top" charoff="50">Norwegian Cognitive NeuroGenetics Study</td><td align="left" valign="top" charoff="50">Norway</td><td align="char" valign="top" char="." charoff="50">625</td><td align="char" valign="top" char="." charoff="50">47.6</td><td align="char" valign="top" char="." charoff="50">18.3</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">79</td><td align="char" valign="top" char="." charoff="50">214</td><td align="char" valign="top" char="." charoff="50">0.34</td></tr><tr><td align="left" valign="top" charoff="50">PNC</td><td align="left" valign="top" charoff="50">Philadelphia Neurodevelopmental Cohort</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">4711</td><td align="char" valign="top" char="." charoff="50">13.8</td><td align="char" valign="top" char="." charoff="50">3.6</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">2440</td><td align="char" valign="top" char="." charoff="50">0.52</td></tr><tr><td align="left" valign="top" charoff="50">TOP</td><td align="left" valign="top" charoff="50">Thematic Organized Psychosis Research Study</td><td align="left" valign="top" charoff="50">Norway</td><td align="char" valign="top" char="." charoff="50">661</td><td align="char" valign="top" char="." charoff="50">31.9</td><td align="char" valign="top" char="." charoff="50">8.9</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">55</td><td align="char" valign="top" char="." charoff="50">359</td><td align="char" valign="top" char="." charoff="50">0.54</td></tr><tr><td align="left" valign="top" charoff="50">ZHH</td><td align="left" valign="top" charoff="50">Zucker Hillside Hospital</td><td align="left" valign="top" charoff="50">USA</td><td align="char" valign="top" char="." charoff="50">187</td><td align="char" valign="top" char="." charoff="50">35.2</td><td align="char" valign="top" char="." charoff="50">18.8</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">78</td><td align="char" valign="top" char="." charoff="50">108</td><td align="char" valign="top" char="." charoff="50">0.58</td></tr></tbody></table></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Results of gene analysis (top 20 genes)</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Symbol</italic></th><th align="left" valign="top" charoff="50"><italic>Gene name</italic></th><th align="left" valign="top" charoff="50"><italic>Chr</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Start</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Stop</italic></th><th align="center" valign="top" char="." charoff="50"><italic>SNPs</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Parameters</italic></th><th align="center" valign="top" char="." charoff="50">N</th><th align="center" valign="top" char="." charoff="50">Z <italic>stat</italic></th><th align="center" valign="top" charoff="50">P<italic>-value</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><italic><bold>WNT3</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Wingless-type MMTV integration site family, member 3</bold></td><td align="left" valign="top" charoff="50"><bold>17q21.31</bold></td><td align="char" valign="top" char="." charoff="50"><bold>44836686</bold></td><td align="char" valign="top" char="." charoff="50"><bold>44901082</bold></td><td align="char" valign="top" char="." charoff="50"><bold>127</bold></td><td align="char" valign="top" char="." charoff="50"><bold>46</bold></td><td align="char" valign="top" char="." charoff="50"><bold>29 063</bold></td><td align="char" valign="top" char="." charoff="50"><bold>5.4753</bold></td><td align="left" valign="top" charoff="50"><bold>2.18E−08</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>PLEKHM1</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Pleckstrin homology and RUN domain-containing M1</bold></td><td align="left" valign="top" charoff="50"><bold>17q21.31</bold></td><td align="char" valign="top" char="." charoff="50"><bold>43508266</bold></td><td align="char" valign="top" char="." charoff="50"><bold>43573146</bold></td><td align="char" valign="top" char="." charoff="50"><bold>123</bold></td><td align="char" valign="top" char="." charoff="50"><bold>23</bold></td><td align="char" valign="top" char="." charoff="50"><bold>27 885</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.9724</bold></td><td align="left" valign="top" charoff="50"><bold>3.31E−07</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>TP53</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Tumor protein p53</bold></td><td align="left" valign="top" charoff="50"><bold>17p13.1</bold></td><td align="char" valign="top" char="." charoff="50"><bold>7566720</bold></td><td align="char" valign="top" char="." charoff="50"><bold>7595863</bold></td><td align="char" valign="top" char="." charoff="50"><bold>94</bold></td><td align="char" valign="top" char="." charoff="50"><bold>32</bold></td><td align="char" valign="top" char="." charoff="50"><bold>31 813</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.9082</bold></td><td align="left" valign="top" charoff="50"><bold>4.60E−07</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>ARHGAP27</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Rho GTPase-activating protein 27</bold></td><td align="left" valign="top" charoff="50"><bold>17q21.31</bold></td><td align="char" valign="top" char="." charoff="50"><bold>43466268</bold></td><td align="char" valign="top" char="." charoff="50"><bold>43515282</bold></td><td align="char" valign="top" char="." charoff="50"><bold>128</bold></td><td align="char" valign="top" char="." charoff="50"><bold>17</bold></td><td align="char" valign="top" char="." charoff="50"><bold>25 183</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.8923</bold></td><td align="left" valign="top" charoff="50"><bold>4.98E−07</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>CYB561D1</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Cytochrome b561 family, member D1</bold></td><td align="left" valign="top" charoff="50"><bold>1p13.3</bold></td><td align="char" valign="top" char="." charoff="50"><bold>110031658</bold></td><td align="char" valign="top" char="." charoff="50"><bold>110048063</bold></td><td align="char" valign="top" char="." charoff="50"><bold>27</bold></td><td align="char" valign="top" char="." charoff="50"><bold>12</bold></td><td align="char" valign="top" char="." charoff="50"><bold>31 670</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.7687</bold></td><td align="left" valign="top" charoff="50"><bold>9.27E−07</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>WRAP53</bold></italic></td><td align="left" valign="top" charoff="50"><bold>WD repeat containing, antisense to TP53</bold></td><td align="left" valign="top" charoff="50"><bold>17p13.1</bold></td><td align="char" valign="top" char="." charoff="50"><bold>7584389</bold></td><td align="char" valign="top" char="." charoff="50"><bold>7611820</bold></td><td align="char" valign="top" char="." charoff="50"><bold>63</bold></td><td align="char" valign="top" char="." charoff="50"><bold>20</bold></td><td align="char" valign="top" char="." charoff="50"><bold>32 133</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.6221</bold></td><td align="left" valign="top" charoff="50"><bold>1.90E−06</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic><bold>ATXN7L2</bold></italic></td><td align="left" valign="top" charoff="50"><bold>Ataxin 7-like 2</bold></td><td align="left" valign="top" charoff="50"><bold>1p13.3</bold></td><td align="char" valign="top" char="." charoff="50"><bold>110021561</bold></td><td align="char" valign="top" char="." charoff="50"><bold>110040426</bold></td><td align="char" valign="top" char="." charoff="50"><bold>29</bold></td><td align="char" valign="top" char="." charoff="50"><bold>11</bold></td><td align="char" valign="top" char="." charoff="50"><bold>33 153</bold></td><td align="char" valign="top" char="." charoff="50"><bold>4.5842</bold></td><td align="left" valign="top" charoff="50"><bold>2.28E−06</bold></td></tr><tr><td align="left" valign="top" charoff="50"><italic>PSMA5</italic></td><td align="left" valign="top" charoff="50">Proteasome subunit alpha 5</td><td align="left" valign="top" charoff="50">1p13.3</td><td align="char" valign="top" char="." charoff="50">109936653</td><td align="char" valign="top" char="." charoff="50">109974108</td><td align="char" valign="top" char="." charoff="50">62</td><td align="char" valign="top" char="." charoff="50">23</td><td align="char" valign="top" char="." charoff="50">32 881</td><td align="char" valign="top" char="." charoff="50">4.4835</td><td align="left" valign="top" charoff="50">3.67E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>NSF</italic></td><td align="left" valign="top" charoff="50">N-ethylmaleimide sensitive factor</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">44663035</td><td align="char" valign="top" char="." charoff="50">44839830</td><td align="char" valign="top" char="." charoff="50">89</td><td align="char" valign="top" char="." charoff="50">20</td><td align="char" valign="top" char="." charoff="50">29 574</td><td align="char" valign="top" char="." charoff="50">4.4412</td><td align="left" valign="top" charoff="50">4.47E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>SORT1</italic></td><td align="left" valign="top" charoff="50">Sortilin 1</td><td align="left" valign="top" charoff="50">1p13.3</td><td align="char" valign="top" char="." charoff="50">109847187</td><td align="char" valign="top" char="." charoff="50">109945563</td><td align="char" valign="top" char="." charoff="50">147</td><td align="char" valign="top" char="." charoff="50">36</td><td align="char" valign="top" char="." charoff="50">33 175</td><td align="char" valign="top" char="." charoff="50">4.4403</td><td align="left" valign="top" charoff="50">4.49E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>SYPL2</italic></td><td align="left" valign="top" charoff="50">Synaptophysin-like 2</td><td align="left" valign="top" charoff="50">1p13.3</td><td align="char" valign="top" char="." charoff="50">110004100</td><td align="char" valign="top" char="." charoff="50">110029764</td><td align="char" valign="top" char="." charoff="50">66</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">34 387</td><td align="char" valign="top" char="." charoff="50">4.4171</td><td align="left" valign="top" charoff="50">5.00E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>CFAP99</italic></td><td align="left" valign="top" charoff="50">Cilia- and flagella-associated protein 99</td><td align="left" valign="top" charoff="50">4p16.3</td><td align="char" valign="top" char="." charoff="50">2415701</td><td align="char" valign="top" char="." charoff="50">2469690</td><td align="char" valign="top" char="." charoff="50">171</td><td align="char" valign="top" char="." charoff="50">43</td><td align="char" valign="top" char="." charoff="50">33 195</td><td align="char" valign="top" char="." charoff="50">4.3569</td><td align="left" valign="top" charoff="50">6.60E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>KANSL1</italic></td><td align="left" valign="top" charoff="50">KAT8 regulatory NSL complex subunit 1</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">44102282</td><td align="char" valign="top" char="." charoff="50">44307740</td><td align="char" valign="top" char="." charoff="50">775</td><td align="char" valign="top" char="." charoff="50">22</td><td align="char" valign="top" char="." charoff="50">27 788</td><td align="char" valign="top" char="." charoff="50">4.3536</td><td align="left" valign="top" charoff="50">6.70E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>STH</italic></td><td align="left" valign="top" charoff="50">Saitohin</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">44071616</td><td align="char" valign="top" char="." charoff="50">44082060</td><td align="char" valign="top" char="." charoff="50">56</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">26 909</td><td align="char" valign="top" char="." charoff="50">4.3028</td><td align="left" valign="top" charoff="50">8.43E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>SPPL2C</italic></td><td align="left" valign="top" charoff="50">Signal peptide peptidase-like 2C</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">43917256</td><td align="char" valign="top" char="." charoff="50">43929438</td><td align="char" valign="top" char="." charoff="50">69</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">30 906</td><td align="char" valign="top" char="." charoff="50">4.2974</td><td align="left" valign="top" charoff="50">8.64E−06</td></tr><tr><td align="left" valign="top" charoff="50"><italic>SP140L</italic></td><td align="left" valign="top" charoff="50">SP140 nuclear body protein like</td><td align="left" valign="top" charoff="50">2q37.1</td><td align="char" valign="top" char="." charoff="50">231186894</td><td align="char" valign="top" char="." charoff="50">231273445</td><td align="char" valign="top" char="." charoff="50">365</td><td align="char" valign="top" char="." charoff="50">51</td><td align="char" valign="top" char="." charoff="50">34 250</td><td align="char" valign="top" char="." charoff="50">4.1532</td><td align="left" valign="top" charoff="50">1.64E−05</td></tr><tr><td align="left" valign="top" charoff="50"><italic>LRRC37A</italic></td><td align="left" valign="top" charoff="50">Leucine-rich repeat containing 37A</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">44367497</td><td align="char" valign="top" char="." charoff="50">44420160</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">26 694</td><td align="char" valign="top" char="." charoff="50">4.1414</td><td align="left" valign="top" charoff="50">1.73E−05</td></tr><tr><td align="left" valign="top" charoff="50"><italic>MAPT</italic></td><td align="left" valign="top" charoff="50">Microtubule-associated protein tau</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">43966748</td><td align="char" valign="top" char="." charoff="50">44110700</td><td align="char" valign="top" char="." charoff="50">725</td><td align="char" valign="top" char="." charoff="50">33</td><td align="char" valign="top" char="." charoff="50">29 040</td><td align="char" valign="top" char="." charoff="50">4.079</td><td align="left" valign="top" charoff="50">2.26E−05</td></tr><tr><td align="left" valign="top" charoff="50"><italic>CRHR1</italic></td><td align="left" valign="top" charoff="50">Corticotropin-releasing hormone receptor 1</td><td align="left" valign="top" charoff="50">17q21.31</td><td align="char" valign="top" char="." charoff="50">43692710</td><td align="char" valign="top" char="." charoff="50">43918194</td><td align="char" valign="top" char="." charoff="50">1024</td><td align="char" valign="top" char="." charoff="50">75</td><td align="char" valign="top" char="." charoff="50">30 191</td><td align="char" valign="top" char="." charoff="50">3.7486</td><td align="left" valign="top" charoff="50">8.89E−05</td></tr><tr><td align="left" valign="top" charoff="50"><italic>PCDH15</italic></td><td align="left" valign="top" charoff="50">Protocadherin-related 15</td><td align="left" valign="top" charoff="50">10q21.1</td><td align="char" valign="top" char="." charoff="50">55557531</td><td align="char" valign="top" char="." charoff="50">56566051</td><td align="char" valign="top" char="." charoff="50">4082</td><td align="char" valign="top" char="." charoff="50">531</td><td align="char" valign="top" char="." charoff="50">33 480</td><td align="char" valign="top" char="." charoff="50">3.218</td><td align="left" valign="top" charoff="50">6.46E−04</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Abbreviation: SNP, single-nucleotide polymorphism. Genes that are in bold font were significant after genome-wide Bonferroni correction.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl3"><label>Table 3</label><caption><title>Results of genetic correlation using LD score regression</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Genetic correlation with other traits using LD score regression</italic></th><th align="left" valign="top" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="left" valign="top" charoff="50"> </th></tr><tr><th align="left" valign="top" charoff="50"><italic>Group</italic></th><th align="left" valign="top" charoff="50"><italic>Phenotype</italic></th><th align="center" valign="top" char="." charoff="50">r<sub><italic>g</italic></sub></th><th align="char" valign="top" char="." charoff="50"><italic>s.e.</italic></th><th align="char" valign="top" char="." charoff="50">z</th><th align="left" valign="top" charoff="50">P<italic>-value</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Cognition</td><td align="left" valign="top" charoff="50"><italic><bold>Childhood IQ</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.89</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.12</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>7.41</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>1.24E</bold></italic><bold>−</bold><italic><bold>13</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><italic><bold>College degree</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.66</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.07</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>9.98</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>1.88E</bold></italic><bold>−</bold><italic><bold>23</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><italic><bold>Years of education</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.73</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.04</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>16.83</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>1.48E</bold></italic><bold>−</bold><italic><bold>63</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50">Neuropsychiatric</td><td align="left" valign="top" charoff="50"><bold>ADHD</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−0.35</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.16</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−2.14</bold></td><td align="center" valign="top" charoff="50"><bold>3.22E−02</bold></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Alzheimer's</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.13</td><td align="char" valign="top" char="." charoff="50">0.11</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>1.17</td><td align="center" valign="top" charoff="50">2.41E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Anorexia</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.02</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.24</td><td align="center" valign="top" charoff="50">8.08E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><bold>Anxiety</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−0.50</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.19</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−2.57</bold></td><td align="center" valign="top" charoff="50"><bold>1.03E−02</bold></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><italic><bold>Autism</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.28</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.08</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>3.43</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>6.00E</bold></italic><bold>−</bold><italic><bold>04</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Bipolar</td><td align="char" valign="top" char="." charoff="50">0.00</td><td align="char" valign="top" char="." charoff="50">0.08</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.06</td><td align="center" valign="top" charoff="50">9.52E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Major depression</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50">0.96</td><td align="center" valign="top" charoff="50">3.35E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><italic><bold>Schizophrenia</bold></italic></td><td align="char" valign="top" char="." charoff="50"><bold>−</bold><italic><bold>0.17</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.05</bold></italic></td><td align="char" valign="top" char="." charoff="50"><bold>−</bold><italic><bold>3.53</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>4.09E</bold></italic><bold>−</bold><italic><bold>04</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50">Personality</td><td align="left" valign="top" charoff="50">Extraversion</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.13</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>1.36</td><td align="center" valign="top" charoff="50">1.74E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Agreeableness</td><td align="char" valign="top" char="." charoff="50">1.24</td><td align="char" valign="top" char="." charoff="50">1.24</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="center" valign="top" charoff="50">3.17E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Conscietousness</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50">0.14</td><td align="char" valign="top" char="." charoff="50">0.74</td><td align="center" valign="top" charoff="50">4.61E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><italic><bold>Openness</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.48</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>0.13</bold></italic></td><td align="char" valign="top" char="." charoff="50"><italic><bold>3.59</bold></italic></td><td align="center" valign="top" charoff="50"><italic><bold>3.25E</bold></italic><bold>−</bold><italic><bold>04</bold></italic></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Neuroticism</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>0.18</td><td align="char" valign="top" char="." charoff="50">0.12</td><td align="char" valign="top" char="." charoff="50"><bold>−</bold>1.49</td><td align="center" valign="top" charoff="50">1.35E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50">Smoking</td><td align="left" valign="top" charoff="50">Age of onset</td><td align="char" valign="top" char="." charoff="50">0.21</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">1.67</td><td align="center" valign="top" charoff="50">9.49E<bold>−</bold>02</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Cigarettes per day</td><td align="char" valign="top" char="." charoff="50">0.03</td><td align="char" valign="top" char="." charoff="50">0.11</td><td align="char" valign="top" char="." charoff="50">0.27</td><td align="center" valign="top" charoff="50">7.85E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><bold>Ever smoker</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−0.24</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.08</bold></td><td align="char" valign="top" char="." charoff="50"><bold>−3.07</bold></td><td align="center" valign="top" charoff="50"><bold>2.13E−03</bold></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><bold>Former smoker</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.29</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.10</bold></td><td align="char" valign="top" char="." charoff="50"><bold>2.80</bold></td><td align="center" valign="top" charoff="50"><bold>5.09E−03</bold></td></tr><tr><td align="left" valign="top" charoff="50">Brain volume</td><td align="left" valign="top" charoff="50">Accumbens</td><td align="char" valign="top" char="." charoff="50">0.26</td><td align="char" valign="top" char="." charoff="50">0.15</td><td align="char" valign="top" char="." charoff="50">1.74</td><td align="center" valign="top" charoff="50">8.18E<bold>−</bold>02</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Caudate</td><td align="char" valign="top" char="." charoff="50">0.08</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50">0.79</td><td align="center" valign="top" charoff="50">4.30E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Hippocampus</td><td align="char" valign="top" char="." charoff="50">0.24</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">1.88</td><td align="center" valign="top" charoff="50">6.06E<bold>−</bold>02</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Intracranial volume</td><td align="char" valign="top" char="." charoff="50">0.14</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">1.09</td><td align="center" valign="top" charoff="50">2.77E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Pallidum</td><td align="char" valign="top" char="." charoff="50">0.16</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">1.28</td><td align="center" valign="top" charoff="50">2.02E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Putamen</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">0.09</td><td align="char" valign="top" char="." charoff="50">1.44</td><td align="center" valign="top" charoff="50">1.50E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Thalamus</td><td align="char" valign="top" char="." charoff="50">0.13</td><td align="char" valign="top" char="." charoff="50">0.12</td><td align="char" valign="top" char="." charoff="50">1.07</td><td align="center" valign="top" charoff="50">2.83E<bold>−</bold>01</td></tr><tr><td align="left" valign="top" charoff="50">Early growth</td><td align="left" valign="top" charoff="50"><bold>Birth length</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.20</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.09</bold></td><td align="char" valign="top" char="." charoff="50"><bold>2.13</bold></td><td align="center" valign="top" charoff="50"><bold>3.33E−02</bold></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50"><bold>Birth weight</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.15</bold></td><td align="char" valign="top" char="." charoff="50"><bold>0.05</bold></td><td align="char" valign="top" char="." charoff="50"><bold>2.89</bold></td><td align="center" valign="top" charoff="50"><bold>3.90E−03</bold></td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Infant head Circumference</td><td align="char" valign="top" char="." charoff="50">0.19</td><td align="char" valign="top" char="." charoff="50">0.11</td><td align="char" valign="top" char="." charoff="50">1.69</td><td align="center" valign="top" charoff="50">9.04E<bold>−</bold>02</td></tr></tbody></table><table-wrap-foot><fn id="t3-fn1"><p>Abbreviations: ADHD, attention-deficit/hyperactivity disorder; IQ, intelligence quotient; LD, linkage disequilibrium. Traits that are in bold font were nominally significant (<italic>P</italic><0.05); traits that are italicized were significant after Bonferroni correction.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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