Population Substructure and Control Selection in Genome-Wide Association Studies

doi:10.1371/journal.pone.0002551

CORC > 数学与系统科学研究院 > 中国科学院数学与系统科学研究院 > 系统科学研究所

	Population Substructure and Control Selection in Genome-Wide Association Studies
	Yu, Kai 1; Wang, Zhaoming 1,2; Li, Qizhai1,3 ; Wacholder, Sholom 1; Hunter, David J.1,4; Hoover, Robert N.1; Chanock, Stephen 1; Thomas, Gilles 1
刊名	PLOS ONE
	2008-07-02
卷号	3 期号:7 页码:14
ISSN号	1932-6203
DOI	10.1371/journal.pone.0002551
英文摘要	Determination of the relevance of both demanding classical epidemiologic criteria for control selection and robust handling of population stratification ( PS) represents a major challenge in the design and analysis of genome-wide association studies (GWAS). Empirical data from two GWAS in European Americans of the Cancer Genetic Markers of Susceptibility (CGEMS) project were used to evaluate the impact of PS in studies with different control selection strategies. In each of the two original case-control studies nested in corresponding prospective cohorts, a minor confounding effect due to PS ( inflation factor lambda of 1.025 and 1.005) was observed. In contrast, when the control groups were exchanged to mimic a cost-effective but theoretically less desirable control selection strategy, the confounding effects were larger (lambda of 1.090 and 1.062). A panel of 12,898 autosomal SNPs common to both the Illumina and Affymetrix commercial platforms and with low local background linkage disequilibrium (pair-wise r(2)< 0.004) was selected to infer population substructure with principal component analysis. A novel permutation procedure was developed for the correction of PS that identified a smaller set of principal components and achieved a better control of type I error (to lambda of 1.032 and 1.006, respectively) than currently used methods. The overlap between sets of SNPs in the bottom 5% of p-values based on the new test and the test without PS correction was about 80%, with the majority of discordant SNPs having both ranks close to the threshold. Thus, for the CGEMS GWAS of prostate and breast cancer conducted in European Americans, PS does not appear to be a major problem in well-designed studies. A study using suboptimal controls can have acceptable type I error when an effective strategy for the correction of PS is employed.
资助项目	Intramural Research Program of the Division of Cancer Epidemiology and Genetics ; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS[N01-CO-12400] ; US NIH[CA65725] ; US NIH[CA87969] ; US NIH[CA49449] ; US NIH[CA67262] ; US NIH[CA50385] ; US NIH[5UO1CA098233]
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000263288200019
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/6837]
专题	系统科学研究所
通讯作者	Yu, Kai
作者单位	1.NCI, Div Canc Epidemiol & Genet, Rockville, MD USA 2.Natl Canc Inst Frederick, SAIC Frederick Inc, Advanced Technol Program, Core Genotyping Facility, Frederick, MD USA 3.Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China 4.Harvard Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA USA
推荐引用方式 GB/T 7714	Yu, Kai,Wang, Zhaoming,Li, Qizhai,et al. Population Substructure and Control Selection in Genome-Wide Association Studies[J]. PLOS ONE,2008,3(7):14.
APA	Yu, Kai.,Wang, Zhaoming.,Li, Qizhai.,Wacholder, Sholom.,Hunter, David J..,...&Thomas, Gilles.(2008).Population Substructure and Control Selection in Genome-Wide Association Studies.PLOS ONE,3(7),14.
MLA	Yu, Kai,et al."Population Substructure and Control Selection in Genome-Wide Association Studies".PLOS ONE 3.7(2008):14.