Journal
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
Volume 49, Issue 9, Pages 884-897Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jaac.2010.06.008
Keywords
ADHD; meta-analysis; association; GWAS; genetics
Categories
Funding
- US National of Institute of Health [R13MH059126, R01MH62873, U01MH085518, R01MH081803, U01MH085515, K23MH066275-01, R01MH58277]
- Children's Hospital of Philadelphia [200710 B]
- NHMRC (Australia)
- Sidney Sax Public Health Fellowship [443036]
- UMC Utrecht Genvlag Grant
- Radboud University, Nijmegen Medical Centre
- Deutsche Forschungsgemeinschaft [KFO 125, SFB 581, GRK 1156, ME 1923/5-1, ME 1923/5-3, GRK 1389, SCHA 542/10-3]
- Bundesministerium fur Bildung und Forschung [BMBF 01GV0605]
- Foundation for the NIH [R01MH080403]
- NWO [480-05-003]
- Dutch Brain Foundation
- Medical Research Council [G9817803B, G0801418B, G0801418] Funding Source: researchfish
- MRC [G0801418] Funding Source: UKRI
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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. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(9):884-897.
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