Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.
Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.
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DOI：
10.1016/j.jaac.2010.06.008
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发表时间：
2010-09
影响因子：
13.3
通讯作者：
Psychiatric GWAS Consortium: ADHD Subgroup
中科院分区：
文献类型：
--
作者：
Neale BM;Medland SE;Ripke S;Asherson P;Franke B;Lesch KP;Faraone SV;Nguyen TT;Schäfer H;Holmans P;Daly M;Steinhausen HC;Freitag C;Reif A;Renner TJ;Romanos M;Romanos J;Walitza S;Warnke A;Meyer J;Palmason H;Buitelaar J;Vasquez AA;Lambregts-Rommelse N;Gill M;Anney RJ;Langely K;O'Donovan M;Williams N;Owen M;Thapar A;Kent L;Sergeant J;Roeyers H;Mick E;Biederman J;Doyle A;Smalley S;Loo S;Hakonarson H;Elia J;Todorov A;Miranda A;Mulas F;Ebstein RP;Rothenberger A;Banaschewski T;Oades RD;Sonuga-Barke E;McGough J;Nisenbaum L;Middleton F;Hu X;Nelson S;Psychiatric GWAS Consortium: ADHD Subgroup
尽管双胞胎和家族研究表明注意缺陷/多动障碍（ADHD）具有高度遗传性，但在全基因组显著水平上影响该性状的基因变异尚未被确定。由于先前的全基因组关联扫描（GWAS）未得出显著结果，我们对现有研究进行了荟萃分析以提高统计效力。
我们使用了来自四个项目的数据：a）费城儿童医院（CHOP），b）国际多中心ADHD遗传学项目（IMAGE）的第一阶段，c）IMAGE的第二阶段（IMAGE II），以及d）由辉瑞公司资助、来自加利福尼亚大学洛杉矶分校、华盛顿大学和麻省总医院的研究（PUWMa）。最终样本量包括2064个三联体、896例患者和2455名对照。对于每项研究，我们填补了国际人类基因组单体型图（HapMap）中的单核苷酸多态性（SNP），计算了关联检验统计量并将其转换为Z分数，然后在荟萃分析中合并加权Z分数。
尽管对候选基因的分析表明它们可能与该疾病有关，但未发现全基因组显著关联。
鉴于ADHD是一种高度遗传性疾病，我们的阴性结果表明，常见的ADHD风险变异的影响个体而言必定非常小，或者其他类型的变异（例如罕见变异）在该疾病的遗传率中占很大比例。
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 scans (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. 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 the 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 SNPs, computed association test statistics and transformed them to Z-scores, and then combined weighted Z-scores in a meta-analysis. No genome-wide significant associations were found, although an analysis of candidate genes suggests they may be involved in the disorder. 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.
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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：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
11
作者：
Brookes, K.;Xu, X.;Johansson, L.
通讯作者：
Johansson, L.
影响因子：
3
作者：
Faraone, Stephen V;Biederman, Joseph
通讯作者：
Biederman, Joseph
DOI：
10.1016/j.psc.2009.12.004
发表时间：
2010-03
期刊：
The Psychiatric clinics of North America
影响因子：
--
作者：
Faraone SV;Mick E
通讯作者：
Mick E