Pathway Analysis by Adaptive Combination of P-Values
Yu, Kai1; Li, Qizhai1,2; Bergen, Andrew W.3; Pfeiffer, Ruth M.1; Rosenberg, Philip S.1; Caporaso, Neil1; Kraft, Peter4; Chatterjee, Nilanjan1
AbstractIt 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)
Keywordpathway analysis genetic association study permutation procedure
Funding ProjectNIH[U01 DA020830] ; National Cancer Institute ; National Science Foundation of China[10371126]
WOS Research AreaGenetics & Heredity ; Public, Environmental & Occupational Health
WOS SubjectGenetics & Heredity ; Public, Environmental & Occupational Health
WOS IDWOS:000272540600005
Citation statistics
Document Type期刊论文
Corresponding AuthorYu, Kai
Affiliation1.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
Recommended Citation
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Yu, Kai]'s Articles
[Li, Qizhai]'s Articles
[Bergen, Andrew W.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Yu, Kai]'s Articles
[Li, Qizhai]'s Articles
[Bergen, Andrew W.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Yu, Kai]'s Articles
[Li, Qizhai]'s Articles
[Bergen, Andrew W.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.