A Subset-Based Approach Improves Power and Interpretation for the Combined Analysis of Genetic Association Studies of Heterogeneous Traits

被引：183

作者：

Bhattacharjee, Samsiddhi ^{[1
]}

Rajaraman, Preetha ^{[2
]}

Jacobs, Kevin B. ^{[3
]}

Wheeler, William A. ^{[4
]}

Melin, Beatrice S. ^{[5
]}

Hartge, Patricia ^{[6
]}

Yeager, Meredith ^{[3
]}

Chung, Charles C. ^{[7
]}

Chanock, Stephen J. ^{[7
]}

Chatterjee, Nilanjan ^{[1
]}

机构：

[1] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA

[2] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA

[3] NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Gaithersburg, MD 20877 USA

[4] Informat Management Serv Inc, Rockville, MD 20852 USA

[5] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden

[6] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[7] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 90卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; TELOMERASE REVERSE-TRANSCRIPTASE; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER; PROSTATE-CANCER; COMMON VARIANT; BREAST-CANCER; RISK; METAANALYSIS; TERT;

D O I：

10.1016/j.ajhg.2012.03.015

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical approaches for meta-analysis or pooled analysis, however, might not be suitable for such analysis because individual variants are likely to be associated with only a subset of the traits or might demonstrate effects in different directions. We propose a method that exhaustively explores subsets of studies for the presence of true association signals that are in either the same direction or possibly opposite directions. An efficient approximation is used for rapid evaluation of p values. We present two illustrative applications, one for a meta-analysis of separate case-control studies of six distinct cancers and another for pooled analysis of a case-control study of glioma, a class of brain tumors that contains heterogeneous subtypes. Both the applications and additional simulation studies demonstrate that the proposed methods offer improved power and more interpretable results when compared to traditional methods for the analysis of heterogeneous traits. The proposed framework has applications beyond genetic association studies.

引用

页码：821 / 835

页数：15

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