Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
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Résumé
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.
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La notice
- Revue
- American Journal of Psychiatry
- Thématique
- Genetic Associations and Epidemiology
- Domaine
- Biochemistry, Genetics and Molecular Biology
- Établissements canadiens
- —
- Organismes subventionnaires
- State University of New York Upstate Medical UniversityNational Institute of Mental HealthFeinberg School of MedicineUniversity of North Carolina at Chapel HillNational Institutes of HealthUniversity of Illinois at Urbana-ChampaignRheinische Friedrich-Wilhelms-Universität BonnUniversitetet i OsloUniversity of California, San DiegoUniversity of TorontoRadboud UniversiteitTrinity College DublinUniversity College LondonBroad InstituteEli Lilly and CompanyState University of New YorkCardiff UniversityChildren’s Hospital of Wisconsin Research InstituteUniversity of PittsburghUniversity of WashingtonJohns Hopkins UniversityNorthShore University HealthSystemHelsingin YliopistoNederlandse Organisatie voor Wetenschappelijk OnderzoekHarvard UniversityPfizerNorthwestern UniversityMassachusetts General HospitalMcMaster UniversityVirginia Commonwealth UniversityVanderbilt UniversityNorth Carolina State UniversityChildren's Hospital of PhiladelphiaNational Alliance for Research on Schizophrenia and Depression
- Mots-clés
- PsychiatryAssociation (psychology)MedicinePsychologyPsychotherapist
- Résumé présent dans OpenAlex
- oui