Genome‐wide association study in German patients with attention deficit/hyperactivity disorder
Identifieur interne : 001A25 ( Istex/Corpus ); précédent : 001A24; suivant : 001A26Genome‐wide association study in German patients with attention deficit/hyperactivity disorder
Auteurs : Anke Hinney ; André Scherag ; Ivonne Jarick ; Özgür Albayrak ; Carolin Pütter ; Sonali Pechlivanis ; Maria R. Dauvermann ; Sebastian Beck ; Heike Weber ; Susann Scherag ; Trang T. Nguyen ; Anna-Lena Volckmar ; Nadja Knoll ; Stephen V. Faraone ; Benjamin M. Neale ; Barbara Franke ; Sven Cichon ; Per Hoffmann ; Markus M. Nöthen ; Stefan Schreiber ; Karl-Heinz Jöckel ; H. Rich Wichmann ; Christine Freitag ; Thomas Lempp ; Jobst Meyer ; Susanne Gilsbach ; Beate Herpertz-Dahlmann ; Judith Sinzig ; Gerd Lehmkuhl ; Tobias J. Renner ; Andreas Warnke ; Marcel Romanos ; Klaus-Peter Lesch ; Andreas Reif ; Benno G. Schimmelmann ; Johannes HebebrandSource :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2011-12.
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Abstract
The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.
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DOI: 10.1002/ajmg.b.31246
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title><author><name sortKey="Hinney, Anke" sort="Hinney, Anke" uniqKey="Hinney A" first="Anke" last="Hinney">Anke Hinney</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Scherag, Andre" sort="Scherag, Andre" uniqKey="Scherag A" first="André" last="Scherag">André Scherag</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Jarick, Ivonne" sort="Jarick, Ivonne" uniqKey="Jarick I" first="Ivonne" last="Jarick">Ivonne Jarick</name><affiliation><mods:affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Albayrak, Ozgur" sort="Albayrak, Ozgur" uniqKey="Albayrak O" first="Özgür" last="Albayrak">Özgür Albayrak</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Putter, Carolin" sort="Putter, Carolin" uniqKey="Putter C" first="Carolin" last="Pütter">Carolin Pütter</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Pechlivanis, Sonali" sort="Pechlivanis, Sonali" uniqKey="Pechlivanis S" first="Sonali" last="Pechlivanis">Sonali Pechlivanis</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dauvermann, Maria R" sort="Dauvermann, Maria R" uniqKey="Dauvermann M" first="Maria R." last="Dauvermann">Maria R. Dauvermann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Beck, Sebastian" sort="Beck, Sebastian" uniqKey="Beck S" first="Sebastian" last="Beck">Sebastian Beck</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Weber, Heike" sort="Weber, Heike" uniqKey="Weber H" first="Heike" last="Weber">Heike Weber</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Scherag, Susann" sort="Scherag, Susann" uniqKey="Scherag S" first="Susann" last="Scherag">Susann Scherag</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nguyen, Trang T" sort="Nguyen, Trang T" uniqKey="Nguyen T" first="Trang T." last="Nguyen">Trang T. Nguyen</name><affiliation><mods:affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Volckmar, Anna Ena" sort="Volckmar, Anna Ena" uniqKey="Volckmar A" first="Anna-Lena" last="Volckmar">Anna-Lena Volckmar</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Knoll, Nadja" sort="Knoll, Nadja" uniqKey="Knoll N" first="Nadja" last="Knoll">Nadja Knoll</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Faraone, Stephen V" sort="Faraone, Stephen V" uniqKey="Faraone S" first="Stephen V." last="Faraone">Stephen V. Faraone</name><affiliation><mods:affiliation>Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York</mods:affiliation></affiliation></author><author><name sortKey="Neale, Benjamin M" sort="Neale, Benjamin M" uniqKey="Neale B" first="Benjamin M." last="Neale">Benjamin M. Neale</name><affiliation><mods:affiliation>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts</mods:affiliation></affiliation></author><author><name sortKey="Franke, Barbara" sort="Franke, Barbara" uniqKey="Franke B" first="Barbara" last="Franke">Barbara Franke</name><affiliation><mods:affiliation>Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Cichon, Sven" sort="Cichon, Sven" uniqKey="Cichon S" first="Sven" last="Cichon">Sven Cichon</name><affiliation><mods:affiliation>Institute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hoffmann, Per" sort="Hoffmann, Per" uniqKey="Hoffmann P" first="Per" last="Hoffmann">Per Hoffmann</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M." last="Nöthen">Markus M. Nöthen</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation><mods:affiliation>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</mods:affiliation></affiliation></author><author><name sortKey="Jockel, Karl Einz" sort="Jockel, Karl Einz" uniqKey="Jockel K" first="Karl-Heinz" last="Jöckel">Karl-Heinz Jöckel</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Wichmann, H Rich" sort="Wichmann, H Rich" uniqKey="Wichmann H" first="H. Rich" last="Wichmann">H. Rich Wichmann</name><affiliation><mods:affiliation>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Freitag, Christine" sort="Freitag, Christine" uniqKey="Freitag C" first="Christine" last="Freitag">Christine Freitag</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lempp, Thomas" sort="Lempp, Thomas" uniqKey="Lempp T" first="Thomas" last="Lempp">Thomas Lempp</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Meyer, Jobst" sort="Meyer, Jobst" uniqKey="Meyer J" first="Jobst" last="Meyer">Jobst Meyer</name><affiliation><mods:affiliation>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Gilsbach, Susanne" sort="Gilsbach, Susanne" uniqKey="Gilsbach S" first="Susanne" last="Gilsbach">Susanne Gilsbach</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Herpertz Ahlmann, Beate" sort="Herpertz Ahlmann, Beate" uniqKey="Herpertz Ahlmann B" first="Beate" last="Herpertz-Dahlmann">Beate Herpertz-Dahlmann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sinzig, Judith" sort="Sinzig, Judith" uniqKey="Sinzig J" first="Judith" last="Sinzig">Judith Sinzig</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lehmkuhl, Gerd" sort="Lehmkuhl, Gerd" uniqKey="Lehmkuhl G" first="Gerd" last="Lehmkuhl">Gerd Lehmkuhl</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</mods:affiliation></affiliation></author><author><name sortKey="Renner, Tobias J" sort="Renner, Tobias J" uniqKey="Renner T" first="Tobias J." last="Renner">Tobias J. Renner</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Warnke, Andreas" sort="Warnke, Andreas" uniqKey="Warnke A" first="Andreas" last="Warnke">Andreas Warnke</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Romanos, Marcel" sort="Romanos, Marcel" uniqKey="Romanos M" first="Marcel" last="Romanos">Marcel Romanos</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lesch, Klaus Eter" sort="Lesch, Klaus Eter" uniqKey="Lesch K" first="Klaus-Peter" last="Lesch">Klaus-Peter Lesch</name><affiliation><mods:affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name><affiliation><mods:affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schimmelmann, Benno G" sort="Schimmelmann, Benno G" uniqKey="Schimmelmann B" first="Benno G." last="Schimmelmann">Benno G. Schimmelmann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Hebebrand, Johannes" sort="Hebebrand, Johannes" uniqKey="Hebebrand J" first="Johannes" last="Hebebrand">Johannes Hebebrand</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1002/ajmg.b.31246</idno><idno type="url">https://api.istex.fr/document/E2378FE797C80441EE8EF5CBC324FFFC2CE70D67/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001A25</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001A25</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title><author><name sortKey="Hinney, Anke" sort="Hinney, Anke" uniqKey="Hinney A" first="Anke" last="Hinney">Anke Hinney</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Scherag, Andre" sort="Scherag, Andre" uniqKey="Scherag A" first="André" last="Scherag">André Scherag</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Jarick, Ivonne" sort="Jarick, Ivonne" uniqKey="Jarick I" first="Ivonne" last="Jarick">Ivonne Jarick</name><affiliation><mods:affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Albayrak, Ozgur" sort="Albayrak, Ozgur" uniqKey="Albayrak O" first="Özgür" last="Albayrak">Özgür Albayrak</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Putter, Carolin" sort="Putter, Carolin" uniqKey="Putter C" first="Carolin" last="Pütter">Carolin Pütter</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Pechlivanis, Sonali" sort="Pechlivanis, Sonali" uniqKey="Pechlivanis S" first="Sonali" last="Pechlivanis">Sonali Pechlivanis</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dauvermann, Maria R" sort="Dauvermann, Maria R" uniqKey="Dauvermann M" first="Maria R." last="Dauvermann">Maria R. Dauvermann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Beck, Sebastian" sort="Beck, Sebastian" uniqKey="Beck S" first="Sebastian" last="Beck">Sebastian Beck</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Weber, Heike" sort="Weber, Heike" uniqKey="Weber H" first="Heike" last="Weber">Heike Weber</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Scherag, Susann" sort="Scherag, Susann" uniqKey="Scherag S" first="Susann" last="Scherag">Susann Scherag</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nguyen, Trang T" sort="Nguyen, Trang T" uniqKey="Nguyen T" first="Trang T." last="Nguyen">Trang T. Nguyen</name><affiliation><mods:affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Volckmar, Anna Ena" sort="Volckmar, Anna Ena" uniqKey="Volckmar A" first="Anna-Lena" last="Volckmar">Anna-Lena Volckmar</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Knoll, Nadja" sort="Knoll, Nadja" uniqKey="Knoll N" first="Nadja" last="Knoll">Nadja Knoll</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Faraone, Stephen V" sort="Faraone, Stephen V" uniqKey="Faraone S" first="Stephen V." last="Faraone">Stephen V. Faraone</name><affiliation><mods:affiliation>Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York</mods:affiliation></affiliation></author><author><name sortKey="Neale, Benjamin M" sort="Neale, Benjamin M" uniqKey="Neale B" first="Benjamin M." last="Neale">Benjamin M. Neale</name><affiliation><mods:affiliation>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts</mods:affiliation></affiliation></author><author><name sortKey="Franke, Barbara" sort="Franke, Barbara" uniqKey="Franke B" first="Barbara" last="Franke">Barbara Franke</name><affiliation><mods:affiliation>Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Cichon, Sven" sort="Cichon, Sven" uniqKey="Cichon S" first="Sven" last="Cichon">Sven Cichon</name><affiliation><mods:affiliation>Institute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hoffmann, Per" sort="Hoffmann, Per" uniqKey="Hoffmann P" first="Per" last="Hoffmann">Per Hoffmann</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M." last="Nöthen">Markus M. Nöthen</name><affiliation><mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation><mods:affiliation>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</mods:affiliation></affiliation></author><author><name sortKey="Jockel, Karl Einz" sort="Jockel, Karl Einz" uniqKey="Jockel K" first="Karl-Heinz" last="Jöckel">Karl-Heinz Jöckel</name><affiliation><mods:affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Wichmann, H Rich" sort="Wichmann, H Rich" uniqKey="Wichmann H" first="H. Rich" last="Wichmann">H. Rich Wichmann</name><affiliation><mods:affiliation>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Freitag, Christine" sort="Freitag, Christine" uniqKey="Freitag C" first="Christine" last="Freitag">Christine Freitag</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lempp, Thomas" sort="Lempp, Thomas" uniqKey="Lempp T" first="Thomas" last="Lempp">Thomas Lempp</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Meyer, Jobst" sort="Meyer, Jobst" uniqKey="Meyer J" first="Jobst" last="Meyer">Jobst Meyer</name><affiliation><mods:affiliation>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Gilsbach, Susanne" sort="Gilsbach, Susanne" uniqKey="Gilsbach S" first="Susanne" last="Gilsbach">Susanne Gilsbach</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Herpertz Ahlmann, Beate" sort="Herpertz Ahlmann, Beate" uniqKey="Herpertz Ahlmann B" first="Beate" last="Herpertz-Dahlmann">Beate Herpertz-Dahlmann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sinzig, Judith" sort="Sinzig, Judith" uniqKey="Sinzig J" first="Judith" last="Sinzig">Judith Sinzig</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lehmkuhl, Gerd" sort="Lehmkuhl, Gerd" uniqKey="Lehmkuhl G" first="Gerd" last="Lehmkuhl">Gerd Lehmkuhl</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</mods:affiliation></affiliation></author><author><name sortKey="Renner, Tobias J" sort="Renner, Tobias J" uniqKey="Renner T" first="Tobias J." last="Renner">Tobias J. Renner</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Warnke, Andreas" sort="Warnke, Andreas" uniqKey="Warnke A" first="Andreas" last="Warnke">Andreas Warnke</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Romanos, Marcel" sort="Romanos, Marcel" uniqKey="Romanos M" first="Marcel" last="Romanos">Marcel Romanos</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lesch, Klaus Eter" sort="Lesch, Klaus Eter" uniqKey="Lesch K" first="Klaus-Peter" last="Lesch">Klaus-Peter Lesch</name><affiliation><mods:affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Reif, Andreas" sort="Reif, Andreas" uniqKey="Reif A" first="Andreas" last="Reif">Andreas Reif</name><affiliation><mods:affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schimmelmann, Benno G" sort="Schimmelmann, Benno G" uniqKey="Schimmelmann B" first="Benno G." last="Schimmelmann">Benno G. Schimmelmann</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Hebebrand, Johannes" sort="Hebebrand, Johannes" uniqKey="Hebebrand J" first="Johannes" last="Hebebrand">Johannes Hebebrand</name><affiliation><mods:affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="ISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-12">2011-12</date><biblScope unit="volume">156</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="888">888</biblScope><biblScope unit="page" to="897">897</biblScope></imprint><idno type="ISSN">1552-4841</idno></series><idno type="istex">E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</idno><idno type="DOI">10.1002/ajmg.b.31246</idno><idno type="ArticleID">AJMG31246</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4841</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>children</term><term>early onset</term><term>homogeneous</term><term>psychiatric</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Anke Hinney</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</json:string></affiliations></json:item><json:item><name>André Scherag</name><affiliations><json:string>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Ivonne Jarick</name><affiliations><json:string>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</json:string></affiliations></json:item><json:item><name>Özgür Albayrak</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Carolin Pütter</name><affiliations><json:string>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Sonali Pechlivanis</name><affiliations><json:string>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Maria R. Dauvermann</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string><json:string>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</json:string></affiliations></json:item><json:item><name>Sebastian Beck</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Heike Weber</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</json:string></affiliations></json:item><json:item><name>Susann Scherag</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Trang T. Nguyen</name><affiliations><json:string>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</json:string></affiliations></json:item><json:item><name>Anna‐Lena Volckmar</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Nadja Knoll</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>Stephen V. Faraone</name><affiliations><json:string>Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York</json:string></affiliations></json:item><json:item><name>Benjamin M. Neale</name><affiliations><json:string>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts</json:string><json:string>Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts</json:string></affiliations></json:item><json:item><name>Barbara Franke</name><affiliations><json:string>Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</json:string></affiliations></json:item><json:item><name>Sven Cichon</name><affiliations><json:string>Institute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany</json:string><json:string>Institute of Human Genetics, University of Bonn, Bonn, Germany</json:string><json:string>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</json:string></affiliations></json:item><json:item><name>Per Hoffmann</name><affiliations><json:string>Institute of Human Genetics, University of Bonn, Bonn, Germany</json:string><json:string>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</json:string></affiliations></json:item><json:item><name>Markus M. Nöthen</name><affiliations><json:string>Institute of Human Genetics, University of Bonn, Bonn, Germany</json:string><json:string>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</json:string></affiliations></json:item><json:item><name>Stefan Schreiber</name><affiliations><json:string>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</json:string></affiliations></json:item><json:item><name>Karl‐Heinz Jöckel</name><affiliations><json:string>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item><json:item><name>H.‐Erich Wichmann</name><affiliations><json:string>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</json:string></affiliations></json:item><json:item><name>Christine Freitag</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</json:string></affiliations></json:item><json:item><name>Thomas Lempp</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</json:string></affiliations></json:item><json:item><name>Jobst Meyer</name><affiliations><json:string>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</json:string></affiliations></json:item><json:item><name>Susanne Gilsbach</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</json:string></affiliations></json:item><json:item><name>Beate Herpertz‐Dahlmann</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</json:string></affiliations></json:item><json:item><name>Judith Sinzig</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</json:string><json:string>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</json:string></affiliations></json:item><json:item><name>Gerd Lehmkuhl</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</json:string></affiliations></json:item><json:item><name>Tobias J. Renner</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</json:string></affiliations></json:item><json:item><name>Andreas Warnke</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</json:string></affiliations></json:item><json:item><name>Marcel Romanos</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</json:string></affiliations></json:item><json:item><name>Klaus‐Peter Lesch</name><affiliations><json:string>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</json:string></affiliations></json:item><json:item><name>Andreas Reif</name><affiliations><json:string>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</json:string></affiliations></json:item><json:item><name>Benno G. Schimmelmann</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string><json:string>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</json:string></affiliations></json:item><json:item><name>Johannes Hebebrand</name><affiliations><json:string>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>psychiatric</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>children</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>early onset</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>homogeneous</value></json:item></subject><articleId><json:string>AJMG31246</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1730</abstractCharCount><pdfWordCount>8430</pdfWordCount><pdfCharCount>53367</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title><corporate><json:item><name>Psychiatric GWAS Consortium: ADHD subgroup</name></json:item></corporate><refBibs><json:item><host><author></author><title>American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th edition. 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disorder</title></json:item></refBibs><genre><json:string>article</json:string></genre><host><volume>156</volume><publisherId><json:string>AJMG</json:string></publisherId><pages><total>10</total><last>897</last><first>888</first></pages><issn><json:string>1552-4841</json:string></issn><issue>8</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1552-485X</json:string></eissn><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><doi><json:string>10.1002/(ISSN)1552-485X</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/ajmg.b.31246</json:string></doi><id>E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</id><score>0.2641934</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/E2378FE797C80441EE8EF5CBC324FFFC2CE70D67/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/E2378FE797C80441EE8EF5CBC324FFFC2CE70D67/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/E2378FE797C80441EE8EF5CBC324FFFC2CE70D67/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Copyright © 2011 Wiley Periodicals, Inc.</p></availability><date>2011</date></publicationStmt><notesStmt><note type="content">*How to Cite this Article: Hinney A, Scherag A, Jarick I, Albayrak Ö, Pütter C, Pechlivanis S, Dauvermann MR, Beck S, Weber H, Scherag S, Nguyen TT, Volckmar A‐L, Knoll N, Faraone SV, Neale BM, Franke B, Cichon S, Hoffmann P, Nöthen MM, Schreiber S, Jöckel K‐H, Wichmann H‐E, Freitag C, Lempp T, Meyer J, Gilsbach S, Herpertz‐Dahlmann B, Sinzig J, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch K‐P, Reif A, Schimmelmann BG, Hebebrand J, Psychiatric GWAS Consortium: ADHD subgroup. 2011. Genome‐Wide Association Study in German Patients With Attention Deficit/Hyperactivity Disorder. Am J Med Genet Part B 156:888–897.</note><note>German Research Association (DFG) - No. He1446/9‐1; No. KFO 125; No. SFB 581; No. GRK 1156; No. ME 1923/5‐1; No. ME 1923/5‐3; No. GRK 1389; No. SCHA 542/10‐3;</note><note>Bundesministerium für Bildung und Forschung - No. BMBF 01GV0605;</note><note>US National of Institute of Health - No. R13MH059126; No. R01MH62873; No. R01MH081803; No. K23MH066275; No. MH58277;</note><note>University of Pennsylvania CTR - No. UL1‐RR‐024134;</note><note>Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia</note><note>Affymetrix Power Award, 2007</note><note>NHMRC (Australia)</note><note>Sidney Sax Public Health Fellowship - No. 443036;</note><note>Wellcome Trust, UK for sample</note><note>UMC Utrecht Genvlag Grant</note><note>Internal Grant of Radboud University Nijmegen Medical Centre</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title><author><orgName>Psychiatric GWAS Consortium: ADHD subgroup</orgName></author><author xml:id="author-1"><persName><forename type="first">Anke</forename><surname>Hinney</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</affiliation></author><author xml:id="author-2"><persName><forename type="first">André</forename><surname>Scherag</surname></persName><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Ivonne</forename><surname>Jarick</surname></persName><affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Özgür</forename><surname>Albayrak</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Carolin</forename><surname>Pütter</surname></persName><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Sonali</forename><surname>Pechlivanis</surname></persName><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">Maria R.</forename><surname>Dauvermann</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</affiliation></author><author xml:id="author-8"><persName><forename type="first">Sebastian</forename><surname>Beck</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-9"><persName><forename type="first">Heike</forename><surname>Weber</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</affiliation></author><author xml:id="author-10"><persName><forename type="first">Susann</forename><surname>Scherag</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-11"><persName><forename type="first">Trang T.</forename><surname>Nguyen</surname></persName><affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</affiliation></author><author xml:id="author-12"><persName><forename type="first">Anna‐Lena</forename><surname>Volckmar</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-13"><persName><forename type="first">Nadja</forename><surname>Knoll</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-14"><persName><forename type="first">Stephen V.</forename><surname>Faraone</surname></persName><affiliation>Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York</affiliation></author><author xml:id="author-15"><persName><forename type="first">Benjamin M.</forename><surname>Neale</surname></persName><affiliation>Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts</affiliation><affiliation>Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts</affiliation></author><author xml:id="author-16"><persName><forename type="first">Barbara</forename><surname>Franke</surname></persName><affiliation>Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</affiliation></author><author xml:id="author-17"><persName><forename type="first">Sven</forename><surname>Cichon</surname></persName><affiliation>Institute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany</affiliation><affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation></author><author xml:id="author-18"><persName><forename type="first">Per</forename><surname>Hoffmann</surname></persName><affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation></author><author xml:id="author-19"><persName><forename type="first">Markus M.</forename><surname>Nöthen</surname></persName><affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation></author><author xml:id="author-20"><persName><forename type="first">Stefan</forename><surname>Schreiber</surname></persName><affiliation>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</affiliation></author><author xml:id="author-21"><persName><forename type="first">Karl‐Heinz</forename><surname>Jöckel</surname></persName><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation></author><author xml:id="author-22"><persName><forename type="first">H.‐Erich</forename><surname>Wichmann</surname></persName><affiliation>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</affiliation></author><author xml:id="author-23"><persName><forename type="first">Christine</forename><surname>Freitag</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</affiliation></author><author xml:id="author-24"><persName><forename type="first">Thomas</forename><surname>Lempp</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</affiliation></author><author xml:id="author-25"><persName><forename type="first">Jobst</forename><surname>Meyer</surname></persName><affiliation>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</affiliation></author><author xml:id="author-26"><persName><forename type="first">Susanne</forename><surname>Gilsbach</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</affiliation></author><author xml:id="author-27"><persName><forename type="first">Beate</forename><surname>Herpertz‐Dahlmann</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</affiliation></author><author xml:id="author-28"><persName><forename type="first">Judith</forename><surname>Sinzig</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</affiliation><affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</affiliation></author><author xml:id="author-29"><persName><forename type="first">Gerd</forename><surname>Lehmkuhl</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</affiliation></author><author xml:id="author-30"><persName><forename type="first">Tobias J.</forename><surname>Renner</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</affiliation></author><author xml:id="author-31"><persName><forename type="first">Andreas</forename><surname>Warnke</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</affiliation></author><author xml:id="author-32"><persName><forename type="first">Marcel</forename><surname>Romanos</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</affiliation></author><author xml:id="author-33"><persName><forename type="first">Klaus‐Peter</forename><surname>Lesch</surname></persName><affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation></author><author xml:id="author-34"><persName><forename type="first">Andreas</forename><surname>Reif</surname></persName><affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation></author><author xml:id="author-35"><persName><forename type="first">Benno G.</forename><surname>Schimmelmann</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</affiliation></author><author xml:id="author-36"><persName><forename type="first">Johannes</forename><surname>Hebebrand</surname></persName><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation></author></analytic><monogr><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="pISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><idno type="DOI">10.1002/(ISSN)1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-12"></date><biblScope unit="volume">156</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="888">888</biblScope><biblScope unit="page" to="897">897</biblScope></imprint></monogr><idno type="istex">E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</idno><idno type="DOI">10.1002/ajmg.b.31246</idno><idno type="ArticleID">AJMG31246</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>psychiatric</term></item><item><term>children</term></item><item><term>early onset</term></item><item><term>homogeneous</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-07-13">Received</change><change when="2011-09-16">Registration</change><change when="2011-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/E2378FE797C80441EE8EF5CBC324FFFC2CE70D67/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1552-485X</doi><issn type="print">1552-4841</issn><issn type="electronic">1552-485X</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title type="short">Am. J. Med. Genet.</title></titleGroup><selfCitationGroup><citation type="ancestor" xml:id="cit1"><journalTitle>American Journal of Medical Genetics</journalTitle><accessionId ref="info:x-wiley/issn/01487299">0148-7299</accessionId><accessionId ref="info:x-wiley/issn/10968628">1096-8628</accessionId><pubYear year="2004">2004</pubYear></citation></selfCitationGroup></publicationMeta><publicationMeta level="part" position="80"><doi origin="wiley" registered="yes">10.1002/ajmg.b.v156.8</doi><numberingGroup><numbering type="journalVolume" number="156">156</numbering><numbering type="journalIssue">8</numbering></numberingGroup><coverDate startDate="2011-12">December 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="20" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ajmg.b.31246</doi><idGroup><id type="unit" value="AJMG31246"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2011 Wiley Periodicals, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2011-07-13"></event><event type="manuscriptAccepted" date="2011-09-16"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.10 mode:FullText" date="2011-10-21"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-10-19"></event><event type="firstOnline" date="2011-10-19"></event><event type="publishedOnlineFinalForm" date="2011-10-20"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">888</numbering><numbering type="pageLast">897</numbering></numberingGroup><correspondenceTo>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:AJMG.AJMG31246.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="52"></count><count type="wordTotal" number="10080"></count></countGroup><titleGroup><title type="main" xml:lang="en">Genome‐wide association study in German patients with attention deficit/hyperactivity disorder<link href="#fn1"></link></title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Anke</givenNames><familyName>Hinney</familyName></personName><contactDetails><email 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affiliationRef="#af1"><personName><givenNames>Johannes</givenNames><familyName>Hebebrand</familyName></personName></creator><creator xml:id="au37" creatorRole="author" noteRef="#fn2"><groupName>Psychiatric GWAS Consortium: ADHD subgroup </groupName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="DE" type="organization"><unparsedAffiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="CH" 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Massachusetts</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="NL" type="organization"><unparsedAffiliation>Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="DE" type="organization"><unparsedAffiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af15" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af16" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af17" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af18" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af19" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af20" countryCode="DE" type="organization"><unparsedAffiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af21" countryCode="DE" type="organization"><unparsedAffiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">psychiatric</keyword><keyword xml:id="kwd2">children</keyword><keyword xml:id="kwd3">early onset</keyword><keyword xml:id="kwd4">homogeneous</keyword></keywordGroup><fundingInfo><fundingAgency>German Research Association (DFG)</fundingAgency><fundingNumber>He1446/9‐1</fundingNumber><fundingNumber>KFO 125</fundingNumber><fundingNumber>SFB 581</fundingNumber><fundingNumber>GRK 1156</fundingNumber><fundingNumber>ME 1923/5‐1</fundingNumber><fundingNumber>ME 1923/5‐3</fundingNumber><fundingNumber>GRK 1389</fundingNumber><fundingNumber>SCHA 542/10‐3</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Bundesministerium für Bildung und Forschung</fundingAgency><fundingNumber>BMBF 01GV0605</fundingNumber></fundingInfo><fundingInfo><fundingAgency>US National of Institute of Health</fundingAgency><fundingNumber>R13MH059126</fundingNumber><fundingNumber>R01MH62873</fundingNumber><fundingNumber>R01MH081803</fundingNumber><fundingNumber>K23MH066275</fundingNumber><fundingNumber>MH58277</fundingNumber></fundingInfo><fundingInfo><fundingAgency>University of Pennsylvania CTR</fundingAgency><fundingNumber>UL1‐RR‐024134</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Affymetrix Power Award, 2007</fundingAgency></fundingInfo><fundingInfo><fundingAgency>NHMRC (Australia)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Sidney Sax Public Health Fellowship</fundingAgency><fundingNumber>443036</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Wellcome Trust, UK for sample</fundingAgency></fundingInfo><fundingInfo><fundingAgency>UMC Utrecht Genvlag Grant</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Internal Grant of Radboud University Nijmegen Medical Centre</fundingAgency></fundingInfo><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:15524841:media:ajmg31246:AJMG_31246_sm_Suppl-Material"></mediaResource><caption>Supplementary Material</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest <i>P</i>‐values (best <i>P</i>‐value: 8.38 × 10<sup>−7</sup>) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest <i>P</i>‐values (<i>P</i>‐values ≤ 7.57 × 10<sup>−5</sup>) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower <i>P</i>‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>How to Cite this Article: Hinney A, Scherag A, Jarick I, Albayrak Ö, Pütter C, Pechlivanis S, Dauvermann MR, Beck S, Weber H, Scherag S, Nguyen TT, Volckmar A‐L, Knoll N, Faraone SV, Neale BM, Franke B, Cichon S, Hoffmann P, Nöthen MM, Schreiber S, Jöckel K‐H, Wichmann H‐E, Freitag C, Lempp T, Meyer J, Gilsbach S, Herpertz‐Dahlmann B, Sinzig J, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch K‐P, Reif A, Schimmelmann BG, Hebebrand J, Psychiatric GWAS Consortium: ADHD subgroup. 2011. Genome‐Wide Association Study in German Patients With Attention Deficit/Hyperactivity Disorder. Am J Med Genet Part B 156:888–897.</p></note><note xml:id="fn2"><p>Collaborators: Psychiatric GWAS Consortium: ADHD subgroup: Hans‐Christoph Steinhausen (Aalborg, Denmark & Basel, and Zurich Switzerland); Klaus‐Peter Lesch, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, Susanne Walitza, Andreas Warnke, Thuy Trang Nguyen, Helmut Schäfer (Würzburg and Marburg, Germany), Christine Freitag, Jobst Meyer, Haukur Palmason (Frankfurt/Homburg and Trier, Germany), Jan Buitelaar (Radboud University Nijmegen Medical Center, Donders Institute for Brain Cognition and Behavior, Nijmegen, Netherlands), Barbara Franke, Alejandro Arias Vasquez (Nijmegen/Utrecht, The Netherlands), Michael Gill, Richard J.L. Anney (Dublin, Ireland), Kate Langley, Michael O'Donovan, Nigel Williams, Peter Holmans, Michael Owen, Anita Thapar (Cardiff, Wales, UK), Lindsey Kent (St. Andrews, Scotland, UK.), Joseph Sergeant (Amsterdam, The Netherlands), Herbert Roeyers (Gent, Belgium), Philip Asherson (London, UK), Eric Mick, Alysa Doyle, Joseph Biederman, (Boston, USA), Susan Smalley, Sandra Loo (Los Angeles, USA), Hakon Hakonarson, Josephine Elia (Philadelphia, USA), Alexandre Todorov (St. Louis, USA), Ana Miranda (Valencia, Spain), Richard Ebstein (Jerusalem, Israel), Aribert Rothenberger, Tobias Banaschewski (Mannheim/Goettingen, Germany), Robert Oades (Essen, Germany), James McGough (Los Angeles, USA), Frank Middleton (SUNY Upstate Medical University, Syracuse, NY), Xiaolan Hu (Pfizer, Groton, CT), Stan Nelson (UCLA, Los Angeles, CA), Benjamin M Neale (Boston, MA), Stephen V. Faraone (SUNY Upstate Medical University, Syracuse, NY, Chair).</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Genome‐wide association study in German patients with attention deficit/hyperactivity disorder</title></titleInfo><name type="personal"><namePart type="given">Anke</namePart><namePart type="family">Hinney</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, 45147 Essen, Germany.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">André</namePart><namePart type="family">Scherag</namePart><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ivonne</namePart><namePart type="family">Jarick</namePart><affiliation>Institute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Özgür</namePart><namePart type="family">Albayrak</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carolin</namePart><namePart type="family">Pütter</namePart><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of 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type="given">Anna‐Lena</namePart><namePart type="family">Volckmar</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nadja</namePart><namePart type="family">Knoll</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen V.</namePart><namePart type="family">Faraone</namePart><affiliation>Medical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Benjamin M.</namePart><namePart type="family">Neale</namePart><affiliation>Center for Human Genetic Research, 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Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Per</namePart><namePart type="family">Hoffmann</namePart><affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Markus M.</namePart><namePart type="family">Nöthen</namePart><affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</affiliation><affiliation>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stefan</namePart><namePart type="family">Schreiber</namePart><affiliation>Institute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karl‐Heinz</namePart><namePart type="family">Jöckel</namePart><affiliation>Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H.‐Erich</namePart><namePart type="family">Wichmann</namePart><affiliation>Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Freitag</namePart><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Lempp</namePart><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jobst</namePart><namePart type="family">Meyer</namePart><affiliation>Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Susanne</namePart><namePart type="family">Gilsbach</namePart><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Beate</namePart><namePart type="family">Herpertz‐Dahlmann</namePart><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Judith</namePart><namePart type="family">Sinzig</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</affiliation><affiliation>Department of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gerd</namePart><namePart type="family">Lehmkuhl</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tobias J.</namePart><namePart type="family">Renner</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andreas</namePart><namePart type="family">Warnke</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marcel</namePart><namePart type="family">Romanos</namePart><affiliation>Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Klaus‐Peter</namePart><namePart type="family">Lesch</namePart><affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andreas</namePart><namePart type="family">Reif</namePart><affiliation>Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Benno G.</namePart><namePart type="family">Schimmelmann</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><affiliation>University Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Johannes</namePart><namePart type="family">Hebebrand</namePart><affiliation>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="corporate"><namePart>Psychiatric GWAS Consortium: ADHD subgroup</namePart><description>Department of Child and Adolescent Psychiatry, University of Duisburg‐Essen, Essen, GermanyInstitute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg‐Essen, Essen, GermanyInstitute for Medical Biometrie and Epidemiologie, Philipps‐University Marburg, Marburg, GermanyUniversity Hospital of Child‐ and Adolescent Psychiatry, University of Bern, Bern, SwitzerlandDepartment of Child and Adolescent Psychiatry, University of Wuerzburg, Wuerzburg, GermanyMedical Genetics Research, Child and Adolescent Psychiatry Research SUNY Upstate Medical University, Syracuse, New YorkCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MassachusettsBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MassachusettsDepartments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsInstitute of Neuroscience and Medicine (INM‐1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, GermanyInstitute of Human Genetics, University of Bonn, Bonn, GermanyDepartment of Genomics, Life & Brain Center, University of Bonn, Bonn, GermanyInstitute of Clinical Molecular Biology, University Hospital Schleswig‐Holstein, Kiel, GermanyInstitute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe‐University Frankfurt am Main, Frankfurt am Main, GermanyDepartment of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen, University Clinics, Aachen, GermanyDepartment of Child and Adolescent Psychiatry, University of Cologne, Cologne, GermanyDepartment of Child and Adolescent Psychiatry and Psychotherapy, LVR – Clinic Bonn, Bonn, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Munich, Munich, GermanyDepartment of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany</description></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-12</dateIssued><dateCaptured encoding="w3cdtf">2011-07-13</dateCaptured><dateValid encoding="w3cdtf">2011-09-16</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">2</extent><extent unit="references">52</extent><extent unit="words">10080</extent></physicalDescription><abstract lang="en">The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and on 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P‐values (best P‐value: 8.38 × 10−7) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P‐values (P‐values ≤ 7.57 × 10−5) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect‐size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta‐analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect‐size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome‐wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P‐values compared to SNPs within random sets of genes of the same size. We did not find genome‐wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD. © 2011 Wiley Periodicals, Inc.</abstract><note type="content">*How to Cite this Article: Hinney A, Scherag A, Jarick I, Albayrak Ö, Pütter C, Pechlivanis S, Dauvermann MR, Beck S, Weber H, Scherag S, Nguyen TT, Volckmar A‐L, Knoll N, Faraone SV, Neale BM, Franke B, Cichon S, Hoffmann P, Nöthen MM, Schreiber S, Jöckel K‐H, Wichmann H‐E, Freitag C, Lempp T, Meyer J, Gilsbach S, Herpertz‐Dahlmann B, Sinzig J, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch K‐P, Reif A, Schimmelmann BG, Hebebrand J, Psychiatric GWAS Consortium: ADHD subgroup. 2011. Genome‐Wide Association Study in German Patients With Attention Deficit/Hyperactivity Disorder. Am J Med Genet Part B 156:888–897.</note><note type="funding">German Research Association (DFG) - No. He1446/9‐1; No. KFO 125; No. SFB 581; No. GRK 1156; No. ME 1923/5‐1; No. ME 1923/5‐3; No. GRK 1389; No. SCHA 542/10‐3; </note><note type="funding">Bundesministerium für Bildung und Forschung - No. BMBF 01GV0605; </note><note type="funding">US National of Institute of Health - No. R13MH059126; No. R01MH62873; No. R01MH081803; No. K23MH066275; No. MH58277; </note><note type="funding">University of Pennsylvania CTR - No. UL1‐RR‐024134; </note><note type="funding">Institutional Development Award to the Center for Applied Genomics from the Children's Hospital of Philadelphia</note><note type="funding">Affymetrix Power Award, 2007</note><note type="funding">NHMRC (Australia)</note><note type="funding">Sidney Sax Public Health Fellowship - No. 443036; </note><note type="funding">Wellcome Trust, UK for sample</note><note type="funding">UMC Utrecht Genvlag Grant</note><note type="funding">Internal Grant of Radboud University Nijmegen Medical Centre</note><subject lang="en"><genre>keywords</genre><topic>psychiatric</topic><topic>children</topic><topic>early onset</topic><topic>homogeneous</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title></titleInfo><genre type="journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supplementary Material - </note><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1552-4841</identifier><identifier type="eISSN">1552-485X</identifier><identifier type="DOI">10.1002/(ISSN)1552-485X</identifier><identifier type="PublisherID">AJMG</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>156</number></detail><detail type="issue"><caption>no.</caption><number>8</number></detail><extent unit="pages"><start>888</start><end>897</end><total>10</total></extent></part></relatedItem><relatedItem type="preceding"><titleInfo><title>American Journal of Medical Genetics</title></titleInfo><identifier type="ISSN">0148-7299</identifier><identifier type="ISSN">1096-8628</identifier><part><date point="end">2004</date></part></relatedItem><identifier type="istex">E2378FE797C80441EE8EF5CBC324FFFC2CE70D67</identifier><identifier type="DOI">10.1002/ajmg.b.31246</identifier><identifier type="ArticleID">AJMG31246</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 Wiley Periodicals, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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