Efficient approximation of P-value of the maximum of correlated tests, with applications to genome-wide association studies | |
Li, Qizhai1,2![]() | |
刊名 | ANNALS OF HUMAN GENETICS
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2008-05-01 | |
卷号 | 72页码:397-406 |
关键词 | MAX robust genome wide scan case control |
ISSN号 | 0003-4800 |
DOI | 10.1111/j.1469-1809.2008.00437.x |
英文摘要 | 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. |
WOS研究方向 | Genetics & Heredity |
语种 | 英语 |
出版者 | BLACKWELL PUBLISHING |
WOS记录号 | WOS:000254927100012 |
内容类型 | 期刊论文 |
源URL | [http://ir.amss.ac.cn/handle/2S8OKBNM/6928] ![]() |
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. |
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