Replication in Genome-Wide Association Studies

被引：224

作者：

Kraft, Peter ^{[1
,2
]}

Zeggini, Eleftheria ^{[3
,4
]}

Ioannidis, John P. A. ^{[5
,6
,7
,8
,9
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[3] Wellcome Trust Sanger Inst, Hinxton, England

[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[5] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[6] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece

[7] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA USA

[8] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Boston, MA USA

[9] Tufts Univ, Sch Med, Boston, MA 02111 USA

来源：

STATISTICAL SCIENCE | 2009年 / 24卷 / 04期

基金：

英国惠康基金;

关键词：

Genome-wide association study; replication; meta-analysis; GENETIC ASSOCIATION; SUSCEPTIBILITY LOCI; PATHWAY APPROACH; COMMON VARIANT; WINNERS CURSE; METAANALYSIS; DISEASE; RISK; HETEROGENEITY; STRATIFICATION;

D O I：

10.1214/09-STS290

中图分类号：

O21 [概率论与数理统计]; C8 [统计学];

学科分类号：

020208 ; 070103 ; 0714 ;

摘要：

Replication helps ensure that a genotype-phenotype association observed in a genome-wide association (GWA) study represents a credible association and is not a chance finding or an artifact due to uncontrolled biases. We discuss prerequisites for exact replication, issues of heterogeneity, advantages and disadvantages of different methods of data synthesis across multiple studies, frequentist vs. Bayesian inferences for replication, and challenges that arise from multi-team collaborations. While consistent replication can greatly improve the credibility of a genotype-phenotype association, it may not eliminate spurious associations due to biases shared by many studies. Conversely, lack of replication in well-powered follow-up studies usually invalidates the initially proposed association, although occasionally it may point to differences in linkage disequilibrium or effect modifiers across studies.

引用

页码：561 / 573

页数：13

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