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Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. Results: No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Conclusions: Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability.

Titel:	Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder
Autor/in / Beteiligte Person:	NEALE, Benjamin M ; MEDLAND, Sarah E ; DALY, Mark ; STEINHAUSEN, Hans-Christoph ; FREITAG, Christine ; REIF, Andreas ; RENNER, Tobias J ; ROMANOS, Marcel ; ROMANOS, Jasmin ; WALITZA, Susanne ; WARNKE, Andreas ; MEYER, Jobst ; RIPKE, Stephan ; PALMASON, Haukur ; BUITELAAR, Jan ; ARIAS VASQUEZ, Alejandro ; LAMBREGTS-ROMMELSE, Nanda ; GILL, Michael ; ANNEY, Richard J. L ; LANGELY, Kate ; O'DONOVAN, Michael ; WILLIAMS, Nigel ; OWEN, Michael ; ASHERSON, Philip ; THAPAR, Anita ; KENT, Lindsey ; SERGEANT, Joseph ; ROEYERS, Herbert ; MICK, Eric ; BIEDERMAN, Joseph ; DOYLE, Alysa ; SMALLEY, Susan ; LOO, Sandra ; HAKONARSON, Hakon ; FRANKE, Barbara ; ELIA, Josephine ; TODOROV, Alexandre ; MIRANDA, Ana ; MULAS, Fernando ; EBSTEIN, Richard P ; ROTHENBERGER, Aribert ; BANASCHEWSKI, Tobias ; OADES, Robert D ; SONUGA-BARKE, Edmund ; MCGOUGH, James ; LESCH, Klaus-Peter ; NISENBAUM, Laura ; MIDDLETON, Frank ; HU, Xiaolan ; NELSON, Stan ; FARAONE, Stephen V ; THUY TRANG, NGUYEN ; SCHÄFER, Helmut ; HOLMANS, Peter ; Psychiatric GWAS Consortium: ADHD Subgroup
Link:	View record from PASCAL Archive
Zeitschrift:	Journal of the American Academy of Child and Adolescent Psychiatry, Jg. 49 (2010), Heft 9, S. 884-897
Veröffentlichung:	Maryland Heights, MO: Elsevier, 2010
Medientyp:	academicJournal
Umfang:	print, 39 ref
ISSN:	0890-8567 (print)
Schlagwort:	Pediatrics Pédiatrie Psychology, psychopathology, psychiatry Psychologie, psychopathologie, psychiatrie Sciences biologiques et medicales Biological and medical sciences Sciences medicales Medical sciences Psychopathologie. Psychiatrie Psychopathology. Psychiatry Etude clinique de l'enfant Child clinical studies Troubles de l'attention. Hyperactivité Attention deficit disorders. Hyperactivity Psychologie. Psychanalyse. Psychiatrie Psychology. Psychoanalysis. Psychiatry PSYCHOPATHOLOGIE. PSYCHIATRIE Article synthèse Review Artículo síntesis Génétique Genetics Genética Métaanalyse Metaanalysis Meta-análisis Trouble déficitaire de l'attention avec hyperactivité Attention disorder with hyperactivity Trastorno por déficit de atención e hiperactividad ADHD GWAS association genetics meta-analysis
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Article File Description: text Language: English Author Affiliations: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, United States ; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States ; Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia ; University of Wuerzburg, Wuerzburg, Germany ; JW Goethe University, Frankfurt am Main, Germany ; Institute of Psychobiology, University of Trier, Trier, Germany ; Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland ; School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom ; Bute Medical School, St. Andrews, Scotland, United Kingdom ; Vrije Universiteit, De Boelelaan, Amsterdam, Netherlands ; Ghent University, Dunantlaan, Ghent, Belgium ; Broad Institute of Harvard and MIT, Cambridge, MA, United States ; Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States ; Clinical and Research Program in Pediatric Psychopharmacology Adult ADHD at Massachusetts General Hospital, Boston, MA, United States ; Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, United States ; The Children's Hospital of Philadelphia, Philadelphia, PA, United States ; University of Pennsylvania, School of Medicine, Philadelphia, PA, United States ; University of Valencia, Spain ; Washington University School of Medicine, St. Louis, MO, United States ; La Fe University Hospital, Faculty of Medicine, Valencia, Spain ; Singapore and Hebrew University, Jerusalem, Israel ; University of Goettingen, Germany ; Clinic for Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany ; MRC Social Genetic and Developmental Psychiatry, Kings' College London, United Kingdom ; School of Psychology, Institute for Disorder on Impulse and Attention, University of Southampton, Highfield, Southampton, and the Child Study Center, New York University, New York, NY, United States ; Eli Lilly and Co., Indianapolis, IN, United States ; Pfizer, Molecular Medicine, Groton, CT, United States ; University of California - Los Angeles, Los Angeles, CA, United States ; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands ; State University of New York Upstate Medical University, Syracuse, New York, NY, United States ; Institut fuer Med. Biometrie und Epidemiologie Philipps-Universitaet Marburg Bunsenstr, Marburg, Germany ; MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Heath Park, Cardiff, United Kingdom ; University of Zurich, Zurich, Switzerland ; Aalborg Psychiatric Hospital, Aarhus University Hospital, Denmark ; Institute of Psychology, University of Basel, Switzerland Rights: Copyright 2015 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Psychopathology. Psychiatry. Clinical psychology ; FRANCIS

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Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder