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

Sven Cichon, Nick Craddock, Mark Daly, Stephen V. Faraone, Pablo V. Gejman, John Kelsoe, Thomas Lehner, Douglas F. Levinson, Audra Moran, Pamela Sklar, Patrick F. Sullivan, Richard Anney, Michael Gill, Aiden Corvin, Jan Buitelaar, Barbara Franke, Josephine Elia, Hakon Hakonarson, Lindsey Kent, James McGoughSusan Smalley, Roel Ophoff, Eric Mick, Susan Santangelo, Manuel Ferreira, Shaun Purcell, Douglas Ruderfer, Jordan Smoller, Roy Perlis, Ben Neale, Jennifer Stone, Laura Nisenbaum, Anita Thapar, Valentina Moskvina, Peter Holmans, Mike O'Donovan, Michael Owen, Richard Todd, Alexandre Todorov, John Rice, Bernie Devlin, Dan Arking, Aravinda Chakravarti, James B. Potash, Ann Pulver, Joseph D. Buxbaum, Edwin Cook, Leena Peltonen, Jaana Suvisaari, Joseph Piven, Danyu Lin, Guy Rouleau, Phillip Awadalla, Gerard Schellenberg, Steve Scherer, James Sutcliffe, Peter Szatmari, Veronica Vieland, Ole A. Andreassen, Arnoldo Frigessi, Douglas Blackwood, Walter Muir, Michael Boehnke, Margit Burmeister, Matthew Flickinger, Weihua Guan, Jun Li, Laura Scott, Rene Breuer, Marcella Rietschel, Thomas Schulze, Tiffany Greenwood, Nicholas Schork, Hugh Gurling, Pierandrea Muglia, Ruchi Upmanyu, Federica Tozzi, Markus Noethen, Thomas Wienker, Michael Steffens, John Nurnberger, Kenneth Kendler, Brien Riley, Edwin van den Oord, Dorret Boomsma, Eco de Geus, Witte Hoogendijk, Brenda Penninx, A. H.M. Willemsen, Danielle Posthuma, William Coryell, Steve Hamilton, Stafam Kloiber, Susanne Lucae, Stephan Ripke, William B. Lawson, Cathryn Lewis, Peter McGuffin, Nick Martin, Naomi Wray, Patrick McGrath, Myrna M. Weissman, James Offord, William A. Scheftner, Susan Slager, Ayman Fanous, Christina Hultman, Sari Kivikko, Claudine Laurent, Todd Lencz, Anil Malhotra, Bryan Mowry, Elizabeth Holliday, Alan Sanders, Sibylle Schwab, Dieter Wildenaver, David St. Clair, Frank Dudbridge, Eve Pickering, Danielle Posthuma, Jonathan Sebat, Jung Ying Tzeng

研究成果: Review article同行評審

339 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)540-556
期刊American Journal of Psychiatry
出版狀態Published - 2009 5月

All Science Journal Classification (ASJC) codes

  • 精神病學和心理健康


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