Genomewide association studies: history, rationale, and prospects for psychiatric disorders.
Genomewide association studies: history, rationale, and prospects for psychiatric disorders.
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DOI：
10.1176/appi.ajp.2008.08091354
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Sullivan PF
中科院分区：
文献类型：
--
作者：
Psychiatric GWAS Consortium Coordinating Committee;Cichon S;Craddock N;Daly M;Faraone SV;Gejman PV;Kelsoe J;Lehner T;Levinson DF;Moran A;Sklar P;Sullivan PF
我们回顾了全基因组关联研究（GWAS）的历史和经验基础，精神疾病GWAS的基本原理，迄今为止的结果，局限性和GWAS荟萃分析的计划。文献综述、把握度分析、问题讨论和计划研究描述。任何两个人之间的大多数基因组DNA序列差异是常见的（频率> 5%）单核苷酸多态性（SNP）。由于相关性的局部模式（连锁不平衡），这些SNP中的500，000 - 1，000，000个可以检验一个或多个常见变异解释疾病遗传风险的假设。GWAS技术还可以检测基因组中的一些拷贝数变异（CNV;缺失和重复）。罕见变异的系统研究将需要大规模的重测序研究。GWAS方法已经检测到数十种常见疾病和性状的大量强大的遗传关联，导致新的病理生理学假设，尽管到目前为止只解释了一小部分遗传变异，并且治疗应用将需要大量的进一步努力。研究设计问题，权力和限制进行了讨论。对于精神疾病，常见的SNP和罕见的CNV有初步的重要发现。许多其他研究正在进行中。大样本的GWAS检测到常见SNP和罕见CNV与精神疾病的关联。可能会有更多的发现-更大的GWAS样本检测到更多的常见易感性变体（影响较小）。精神病学GWAS联盟（由来自54个机构的110名研究人员组成）正在对精神分裂症、双相情感障碍、重度抑郁症、自闭症和注意缺陷多动障碍进行GWAS荟萃分析。根据其他疾病的结果，将需要更大的样本。GWAS的贡献将取决于每种疾病的真正遗传结构。
We review 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. Literature review, power analysis, discussion of issues and description of planned studies. 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), 500,000-1,000,000 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 (CNVs; deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing studies. 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 so 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 rare CNVs. Many other studies are in progress. GWAS of large samples have detected associations of common SNPs and of rare CNVs to psychiatric disorders. More findings are likely -- larger GWAS samples detect larger numbers of common susceptibility variants (with smaller effects). The Psychiatric GWAS Consortium (of 110 researchers from 54 institutions) is carrying out 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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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
7.7
作者：
Freathy RM;Timpson NJ;Lawlor DA;Pouta A;Ben-Shlomo Y;Ruokonen A;Ebrahim S;Shields B;Zeggini E;Weedon MN;Lindgren CM;Lango H;Melzer D;Ferrucci L;Paolisso G;Neville MJ;Karpe F;Palmer CN;Morris AD;Elliott P;Jarvelin MR;Smith GD;McCarthy MI;Hattersley AT;Frayling TM
通讯作者：
Frayling TM
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
影响因子：
30.8
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
通讯作者：
Bertram, Lars
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.