Genetic Background Comparison Using Distance-Based Regression, with Applications in Population Stratification Evaluation and Adjustment

doi:10.1002/gepi.20396

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	Genetic Background Comparison Using Distance-Based Regression, with Applications in Population Stratification Evaluation and Adjustment
	Li, Qizhai1,2 ; Wacholder, Sholom 1; Hunter, David J.1,3; Hoover, Robert N.1; Chanock, Stephen 1; Thomas, Gilles 1; Yu, Kai 1
	2009-07-01
发表期刊	GENETIC EPIDEMIOLOGY
ISSN	0741-0395
卷号	33 期号:5 页码:432-441
摘要	Population stratification (PS) can lead to an inflated rate of false-positive findings in genome-wide association studies (GWAS). The commonly used approach of adjustment for a fixed number of principal components (PCs) could have a deleterious impact on power when selected PCs are equally distributed in cases and controls, or the adjustment of certain covariates, such as self-identified ethnicity or recruitment center, already included in the association analyses, correctly maps to major axes of genetic heterogeneity. We propose a computationally efficient procedure, PC-Finder, to identify a minimal set of PCs while permitting an effective correction for PS. A general pseudo F statistic, derived from a non-parametric multivariate regression model, can be used to assess whether PS exists or has been adequately corrected by a set of selected PCs. Empirical data from two GWAS conducted as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project demonstrate the application of the procedure. Furthermore, simulation studies show the power advantage of the proposed procedure in GWAS over currently used PS correction strategies, particularly when the PCs with substantial genetic variation are distributed similarly in cases and controls and therefore do not induce PS. Genet. Epidemiol. 33:432-441, 2009. Published 2009 Wiley-Liss, Inc.
关键词	population stratification pseudo F statistic distance-based regression
DOI	10.1002/gepi.20396
语种	英语
WOS研究方向	Genetics & Heredity ; Public, Environmental & Occupational Health
WOS类目	Genetics & Heredity ; Public, Environmental & Occupational Health
WOS记录号	WOS:000267605700007
出版者	WILEY-LISS
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/7228
专题	系统科学研究所
通讯作者	Yu, Kai
作者单位	1.NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA 2.Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China 3.Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Li, Qizhai,Wacholder, Sholom,Hunter, David J.,et al. Genetic Background Comparison Using Distance-Based Regression, with Applications in Population Stratification Evaluation and Adjustment[J]. GENETIC EPIDEMIOLOGY,2009,33(5):432-441.
APA	Li, Qizhai.,Wacholder, Sholom.,Hunter, David J..,Hoover, Robert N..,Chanock, Stephen.,...&Yu, Kai.(2009).Genetic Background Comparison Using Distance-Based Regression, with Applications in Population Stratification Evaluation and Adjustment.GENETIC EPIDEMIOLOGY,33(5),432-441.
MLA	Li, Qizhai,et al."Genetic Background Comparison Using Distance-Based Regression, with Applications in Population Stratification Evaluation and Adjustment".GENETIC EPIDEMIOLOGY 33.5(2009):432-441.