Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies

doi:10.1111/j.1469-1809.2008.00437.x

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	Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies
	Li, Qizhai1,2 ; Zheng, Gang 4; Li, Zhaohai 3,5; Yu, Kai 1
	2008-05-01
发表期刊	ANNALS OF HUMAN GENETICS
ISSN	0003-4800
卷号	72 页码:397-406
摘要	Genome-wide association study (GWAS), typically involving 100,000 to 500,000 single-nucleotide polymorphisms (SNPs), is a powerful approach to identify disease susceptibility loci. In a GWAS, single-marker analysis, which tests one SNP at a time, is usually used as the first stage to screen SNPs across the genome in order to identify a small fraction of promising SNPs with relatively low p-values for further and more focused studies. For single-marker analysis, the trend test derived for an additive genetic model is often used. This may not be robust when the additive assumption is not appropriate for the true underlying disease model. A robust test, MAX, based on the maximum of three trend test statistics derived for recessive, additive, and dominant models, has been proposed recently for GWAS. But its p-value has to be evaluated through a resampling-based procedure, which is computationally challenging for the analysis of GWAS. Obtaining the p-value for MAX with adjustment for the covariates can be even more time-consuming. In this article, we provide a simple approximation for the p-value of the MAX test with or without adjusting for the covariates. The new method avoids resampling steps and thus makes the MAX test readily applicable to GWAS. We use simulation studies as well as real datasets on 17 confirmed disease-associated SNPs to assess the accuracy of the proposed method. We also apply the method to the GWAS of coronary artery disease.
关键词	MAX robust genome wide scan case control
DOI	10.1111/j.1469-1809.2008.00437.x
语种	英语
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000254927100012
出版者	BLACKWELL PUBLISHING
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/6929
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, Bethesda, MD 20892 USA 2.Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China 3.George Washington Univ, Dept Stat, Washington, DC 20052 USA 4.NHLBI, Off Biostat Res, Off Director, Bethesda, MD 20892 USA 5.NICHHD, Biomet & Math Stat Branch, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Li, Qizhai,Zheng, Gang,Li, Zhaohai,et al. Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies[J]. ANNALS OF HUMAN GENETICS,2008,72:397-406.
APA	Li, Qizhai,Zheng, Gang,Li, Zhaohai,&Yu, Kai.(2008).Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies.ANNALS OF HUMAN GENETICS,72,397-406.
MLA	Li, Qizhai,et al."Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies".ANNALS OF HUMAN GENETICS 72(2008):397-406.