Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Search for Related Content PubMed Citation Genetics

Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders

OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues discussed, and planned studies assessed. RESULTS: Most of the genomic DNA sequence differences between any two people are common (frequency >5%) single nucleotide polymorphisms (SNPs). Because of localized patterns of correlation (linkage disequilibrium), 500,000 to 1,000,000 of these SNPs can test the hypothesis that one or more common variants explain part of the genetic risk for a disease. GWAS technologies can also detect some of the copy number variants (deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing analyses. GWAS methods have detected a remarkable number of robust genetic associations for dozens of common diseases and traits, leading to new pathophysiological hypotheses, although only small proportions of genetic variance have been explained thus far and therapeutic applications will require substantial further effort. Study design issues, power, and limitations are discussed. For psychiatric disorders, there are initial significant findings for common SNPs and for rare copy number variants, and many other studies are in progress. CONCLUSIONS: GWAS of large samples have detected associations of common SNPs and of rare copy number variants with psychiatric disorders. More findings are likely, since larger GWAS samples detect larger numbers of common susceptibility variants, with smaller effects. The Psychiatric GWAS Consortium is conducting GWAS meta-analyses for schizophrenia, bipolar disorder, major depressive disorder, autism, and attention deficit hyperactivity disorder. Based on results for other diseases, larger samples will be required. The contribution of GWAS will depend on the true genetic architecture of each disorder.

This article has been cited by other articles:

				N. R. Wray and P. M. Visscher Narrowing the Boundaries of the Genetic Architecture of Schizophrenia Schizophr Bull, January 1, 2010; 36(1): 14 - 23. [Abstract] [Full Text] [PDF]

				R. D. Alarcon Pharmacogenomic perspectives on the management of mood disorders The Psychiatrist, October 1, 2009; 33(10): 361 - 363. [Abstract] [Full Text] [PDF]

				K. Panoutsopoulou and E. Zeggini Finding common susceptibility variants for complex disease: past, present and future Briefings in Functional Genomics, September 1, 2009; 8(5): 345 - 352. [Abstract] [Full Text] [PDF]

				J. I. Nurnberger Jr. New Hope for Pharmacogenetic Testing Am J Psychiatry, June 1, 2009; 166(6): 635 - 638. [Full Text] [PDF]

Get information about faster international access.

Privacy Policy

Copyright © 2009 American Psychiatric Association. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us