Pathway Analysis by Adaptive Combination of P-Values

doi:10.1002/gepi.20422

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	Pathway Analysis by Adaptive Combination of P-Values
	Yu, Kai 1; Li, Qizhai 1,2; Bergen, Andrew W.3; Pfeiffer, Ruth M.1; Rosenberg, Philip S.1; Caporaso, Neil 1; Kraft, Peter 4; Chatterjee, Nilanjan 1
	2009-12-01
发表期刊	GENETIC EPIDEMIOLOGY
ISSN	0741-0395
卷号	33 期号:8 页码:700-709
摘要	It is increasingly recognized that pathway analyses-a joint test of association between the outcome and a group of single nucleotide polymorphisms (SNPs) within a biological pathway-could potentially complement single-SNP analysis and provide additional insights for the genetic architecture of complex diseases. Building upon existing P-value combining methods, we propose a class of highly flexible pathway analysis approaches based on an adaptive rank truncated product statistic that can effectively combine evidence of associations over different SNPs and genes within a pathway. The statistical significance of the pathway-level test statistics is evaluated using a highly efficient permutation algorithm that remains computationally feasible irrespective of the size of the pathway and complexity of the underlying test statistics for summarizing SNP- and gene-level associations. We demonstrate through simulation studies that a gene-based analysis that treats the underlying genes, as opposed to the underlying SNPs, as the basic units for hypothesis testing, is a very robust and powerful approach to pathway-based association testing. We also illustrate the advantage of the proposed methods using a study of the association between the nicotinic receptor pathway and cigarette smoking behaviors. Genet. Epidemiol. 33:700-709, 2009. Published 2009 Wiley-Liss, Inc.(dagger)
关键词	pathway analysis genetic association study permutation procedure
DOI	10.1002/gepi.20422
语种	英语
资助项目	NIH[U01 DA020830] ; National Cancer Institute ; National Science Foundation of China[10371126]
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:000272540600005
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/9114
专题	中国科学院数学与系统科学研究院
通讯作者	Yu, Kai
作者单位	1.NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA 2.CAS, Acad Math & Syst Sci, Beijing, Peoples R China 3.SRI Int, Mol Genet Program, Ctr Hlth Sci, Menlo Pk, CA 94025 USA 4.Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Yu, Kai,Li, Qizhai,Bergen, Andrew W.,et al. Pathway Analysis by Adaptive Combination of P-Values[J]. GENETIC EPIDEMIOLOGY,2009,33(8):700-709.
APA	Yu, Kai.,Li, Qizhai.,Bergen, Andrew W..,Pfeiffer, Ruth M..,Rosenberg, Philip S..,...&Chatterjee, Nilanjan.(2009).Pathway Analysis by Adaptive Combination of P-Values.GENETIC EPIDEMIOLOGY,33(8),700-709.
MLA	Yu, Kai,et al."Pathway Analysis by Adaptive Combination of P-Values".GENETIC EPIDEMIOLOGY 33.8(2009):700-709.