Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
20732625
TITLE
Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.
ABSTRACT
OBJECTIVE NlmCategory: 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 NlmCategory: METHODS
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. 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 NlmCategory: RESULTS
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. 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. No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder.
CONCLUSIONS NlmCategory: CONCLUSIONS
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. 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. No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. 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.
2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2010 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2009/12/14
revised 2010/06/01
accepted 2010/06/16
entrez 2010/08/25 06:00
pubmed 2010/08/25 06:00
medline 2010/12/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Neale BM Neale Benjamin M BM Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Medland SE Medland Sarah E SE
Ripke S Ripke Stephan S
Asherson P Asherson Philip P
Franke B Franke Barbara B
Lesch KP Lesch Klaus-Peter KP
Faraone SV Faraone Stephen V SV
Nguyen TT Nguyen Thuy Trang TT
Schäfer H Schäfer Helmut H
Holmans P Holmans Peter P
Daly M Daly Mark M
Steinhausen HC Steinhausen Hans-Christoph HC
Freitag C Freitag Christine C
Reif A Reif Andreas A
Renner TJ Renner Tobias J TJ
Romanos M Romanos Marcel M
Romanos J Romanos Jasmin J
Walitza S Walitza Susanne S
Warnke A Warnke Andreas A
Meyer J Meyer Jobst J
Palmason H Palmason Haukur H
Buitelaar J Buitelaar Jan J
Vasquez AA Vasquez Alejandro Arias AA
Lambregts-Rommelse N Lambregts-Rommelse Nanda N
Gill M Gill Michael M
Anney RJ Anney Richard J L RJ
Langely K Langely Kate K
O'Donovan M O'Donovan Michael M
Williams N Williams Nigel N
Owen M Owen Michael M
Thapar A Thapar Anita A
Kent L Kent Lindsey L
Sergeant J Sergeant Joseph J
Roeyers H Roeyers Herbert H
Mick E Mick Eric E
Biederman J Biederman Joseph J
Doyle A Doyle Alysa A
Smalley S Smalley Susan S
Loo S Loo Sandra S
Hakonarson H Hakonarson Hakon H
Elia J Elia Josephine J
Todorov A Todorov Alexandre A
Miranda A Miranda Ana A
Mulas F Mulas Fernando F
Ebstein RP Ebstein Richard P RP
Rothenberger A Rothenberger Aribert A
Banaschewski T Banaschewski Tobias T
Oades RD Oades Robert D RD
Sonuga-Barke E Sonuga-Barke Edmund E
McGough J McGough James J
Nisenbaum L Nisenbaum Laura L
Middleton F Middleton Frank F
Hu X Hu Xiaolan X
Nelson S Nelson Stan S
Psychiatric GWAS Consortium: ADHD Subgroup
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Neale Benjamin M BM
Medland Sarah E SE
Ripke Stephan S
Asherson Philip P
Franke Barbara B
Lesch Klaus-Peter KP
Faraone Stephen V SV
Medland Sarah E SE
Ripke Stephan S
Nguyen Thuy Trang TT
Schäfer Helmut H
Holmans Peter P
Daly Mark M
Neale Benjamin M BM
Steinhausen Hans-Christoph HC
Lesch Klaus-Peter KP
Freitag Christine C
Reif Andreas A
Renner Tobias J TJ
Romanos Marcel M
Romanos Jasmin J
Walitza Susanne S
Warnke Andreas A
Nguyen Thuy Trang TT
Schäfer Helmut H
Meyer Jobst J
Palmason Haukur H
Buitelaar Jan J
Franke Barbara B
Vasquez Alejandro Arias AA
Lambregts-Rommelse Nanda N
Gill Michael M
Anney Richard J L RJ
Langely Kate K
O'Donovan Michael M
Williams Nigel N
Holmans Peter P
Owen Michael M
Thapar Anita A
Kent Lindsey L
Sergeant Joseph J
Roeyers Herbert H
Asherson Philip P
Mick Eric E
Biederman Joseph J
Doyle Alysa A
Smalley Susan S
Loo Sandra S
Hakonarson Hakon H
Elia Josephine J
Todorov Alexandre A
Miranda Ana A
Mulas Fernando F
Ebstein Richard P RP
Rothenberger Aribert A
Banaschewski Tobias T
Oades Robert D RD
Sonuga-Barke Edmund E
McGough James J
Nisenbaum Laura L
Faraone Stephen V SV
Middleton Frank F
Hu Xiaolan X
Nelson Stan S
Thapar Anita A
McGough James J
Mick Eric E
Neale Benjamin M BM
Faraone Stephen V SV
Neale Benjamin M BM
Daly Mark M
JOURNAL
VOLUME: 49
ISSUE: 9
TITLE: Journal of the American Academy of Child and Adolescent Psychiatry
ISOABBREVIATION: J Am Acad Child Adolesc Psychiatry
YEAR: 2010
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1527-5418
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Am Acad Child Adolesc Psychiatry
COUNTRY: United States
ISSNLINKING: 0890-8567
NLMUNIQUEID: 8704565
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
CommentIn J Am Acad Child Adolesc Psychiatry. 2010 Aug;49(8):729-35 20643308
GRANTS
GRANTID AGENCY COUNTRY
U01 MH085518 NIMH NIH HHS United States
R01 MH058277-03 NIMH NIH HHS United States
R01 MH062873 NIMH NIH HHS United States
U01 MH085515 NIMH NIH HHS United States
R01 MH058277 NIMH NIH HHS United States
R01MH080403 NIMH NIH HHS United States
K23MH066275-01 NIMH NIH HHS United States
R01 MH062873-03 NIMH NIH HHS United States
R13 MH059126 NIMH NIH HHS United States
K23 MH066275 NIMH NIH HHS United States
R01MH62873 NIMH NIH HHS United States
R13MH059126 NIMH NIH HHS United States
U01MH085518 NIMH NIH HHS United States
R01 MH081803 NIMH NIH HHS United States
R01 MH058277-04 NIMH NIH HHS United States
R13 MH059126-09 NIMH NIH HHS United States
R01MH081803 NIMH NIH HHS United States
R01 MH062873-05 NIMH NIH HHS United States
R01MH58277 NIMH NIH HHS United States
K23 MH066275-01A1 NIMH NIH HHS United States
U01MH085515 NIMH NIH HHS United States
R01 MH083823 NIMH NIH HHS United States
R13 MH059126-10 NIMH NIH HHS United States
R01 MH058277-05 NIMH NIH HHS United States
R01 MH080403 NIMH NIH HHS United States
R01 MH062873-01A1 NIMH NIH HHS United States
R01 MH062873-02 NIMH NIH HHS United States
R01 MH058277-02 NIMH NIH HHS United States
U01 MH085518-01 NIMH NIH HHS United States
G0801418 Medical Research Council United Kingdom
Wellcome Trust United Kingdom
R01 MH062873-04 NIMH NIH HHS United States
U01 MH085515-01 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Attention Deficit Disorder with Hyperactivity psychology
Child psychology
Child, Preschool psychology
Female psychology
Genetic Association Studies psychology
Genome-Wide Association Study psychology
Humans psychology
Male psychology
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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