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

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Title: Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder
Language: English
Authors: Neale, Benjamin M., Medland, Sarah E., Ripke, Stephan, Asherson, Philip, Franke, Barbara, Lesch, Klaus-Peter, Faraone, Stephen V., Nguyen, Thuy Trang, Schafer, Helmut, Holmans, Peter, Daly, Mark, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J., Romanos, Marcel, Romanos, Jasmin, Walitza, Susanne, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Buitelaar, Jan, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Gill, Michael, Anney, Richard J. L., Langely, Kate, O'Donovan, Michael, Williams, Nigel, Owen, Michael, Thapar, Anita, Kent, Lindsey, Sergeant, Joseph, Roeyers, Herbert, Mick, Eric, Biederman, Joseph, Doyle, Alysa, Smalley, Susan, Loo, Sandra, Hakonarson, Hakon, Elia, Josephine, Todorov, Alexandre, Miranda, Ana, Mulas, Fernando, Ebstein, Richard P., Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D., Sonuga-Barke, Edmund, McGough, James, Nisenbaum, Laura, Middleton, Frank, Hu, Xiaolan, Nelson, Stan
Source: Journal of the American Academy of Child & Adolescent Psychiatry. Sep 2010 49(9):884-897.
Availability: Elsevier. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. Tel: 877-839-7126; Tel: 407-345-4020; Fax: 407-363-1354; e-mail: usjcs@elsevier.com; Web site: http://www.elsevier.com
Peer Reviewed: Y
Page Count: 14
Publication Date: 2010
Document Type: Journal Articles
Reports - Research
Descriptors: Attention Deficit Hyperactivity Disorder, Hospitals, Association Measures, Genetics, Identification, Universities, Evaluation Methods, Twins, Disabilities
Geographic Terms: California, Pennsylvania
DOI: 10.1016/j.jaac.2010.06.008
ISSN: 0890-8567
Abstract: 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. (Contains 3 figures and 3 tables.)
Abstractor: As Provided
Entry Date: 2011
Accession Number: EJ944568
Database: ERIC
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  Data: 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. (Contains 3 figures and 3 tables.)
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