Evaluation of association tests for rare variants using simulated data sets in the Genetic Analysis Workshop 17 data

We evaluate four association tests for rare variants-the combined multivariate and collapsing (CMC) method, two weighted-sum methods, and a variable threshold method-by applying them to the simulated data sets of unrelated individuals in the Genetic Analysis Workshop 17 (GAW17) data. The family-wise...

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Bibliographic Details
Published in:BMC proceedings 2011, Vol.5 Suppl 9 (Suppl 9), p.S86-S86, Article S86
Main Authors: Chen, Wenan, Gao, Xi, Wang, Jiexun, Sun, Chuanyu, Wan, Wen, Zhi, Degui, Liu, Nianjun, Chen, Xiangning, Gao, Guimin
Format: Article
Language:English
Subjects:
Design
Disease
Genes
Genetics
Genomes
Hypothesis testing
Methods
Multivariate analysis
Normal distribution
Proceedings
Standard deviation
Studies
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Summary:We evaluate four association tests for rare variants-the combined multivariate and collapsing (CMC) method, two weighted-sum methods, and a variable threshold method-by applying them to the simulated data sets of unrelated individuals in the Genetic Analysis Workshop 17 (GAW17) data. The family-wise error rate (FWER) and average power are used as criteria for evaluation. Our results show that when all nonsynonymous SNPs (rare variants and common variants) in a gene are jointly analyzed, the CMC method fails to control the FWER; when only rare variants (single-nucleotide polymorphisms with minor allele frequency less than 0.05) are analyzed, all four methods can control FWER well. All four methods have comparable power, which is low for the analysis of the GAW17 data sets. Three of the methods (not including the CMC method) involve estimation of p-values using permutation procedures that either can be computationally intensive or generate inflated FWERs. We adapt a fast permutation procedure into these three methods. The results show that using the fast permutation procedure can produce FWERs and average powers close to the values obtained from the standard permutation procedure on the GAW17 data sets. The standard permutation procedure is computationally intensive.
ISSN:1753-6561
1753-6561
DOI:10.1186/1753-6561-5-S9-S86