Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies

doi:10.1159/000291927

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	Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies
	Li, Qizhai2 ; Zhang, Hong 1; Yu, Kai 1
	2010
发表期刊	HUMAN HEREDITY
ISSN	0001-5652
卷号	69 期号:4 页码:219-228
摘要	Most current genetic association studies, including genome-wide association studies, look for the single nucleotide polymorphisms (SNPs) with a relatively large minor allele frequency (MAF) (e.g. >5%) in the search for genetic loci underlying the susceptibility for complex diseases. The strategy of focusing on common SNPs in genetic association studies is very effective under the common-disease-common-variant (CDCV) hypothesis, which claims that common diseases are caused by common variants that have relatively small to moderate effects. Although the CDCV hypothesis has become the dogma guiding the conduct of association studies over the past decade, growing evidence from recent empirical data and simulations suggests that the causal genetic polymorphisms, including SNPs and copy number variants (CNVs), for common diseases have a wide spectrum of MAFs, ranging from rare to common. Unlike the analysis for common genetic variants, statistical approaches for the analysis of rare variants receive very little attention. Methods developed for common variants usually rely on their asymptotic properties, which can be inaccurate for the study of the rare variants with limited sample size. Although Fisher's exact test can be used for such a scenario, it is usually conservative and thus its usefulness is diminished to some extent. Here we propose two novel approaches for the analysis of rare genetic variants. Simulation studies and two real examples demonstrate the advantages of the proposed methods over the existing methods. Copyright (C) 2010 S. Karger AG, Basel
关键词	Association test CDRV Rare polymorphisms
DOI	10.1159/000291927
语种	英语
资助项目	National Institutes of Health ; National Young Science Foundation of China[10901155]
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000277281200001
出版者	KARGER
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/10781
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, NIH, Bethesda, MD 20892 USA 2.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Li, Qizhai,Zhang, Hong,Yu, Kai. Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies[J]. HUMAN HEREDITY,2010,69(4):219-228.
APA	Li, Qizhai,Zhang, Hong,&Yu, Kai.(2010).Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies.HUMAN HEREDITY,69(4),219-228.
MLA	Li, Qizhai,et al."Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies".HUMAN HEREDITY 69.4(2010):219-228.