title: MCPerm: a Monte Carlo permutation method for accurately correcting the multiple testing in a meta-analysis of genetic association studies.
abstract: Traditional permutation (TradPerm) tests are usually considered the gold standard for multiple testing corrections. However, they can be difficult to complete for the meta-analyses of genetic association studies based on multiple single nucleotide polymorphism loci as they depend on individual-level genotype and phenotype data to perform random shuffles, which are not easy to obtain. Most meta-analyses have therefore been performed using summary statistics from previously published studies. To carry out a permutation using only genotype counts without changing the size of the TradPerm P-value, we developed a Monte Carlo permutation (MCPerm) method. First, for each study included in the meta-analysis, we used a two-step hypergeometric distribution to generate a random number of genotypes in cases and controls. We then carried out a meta-analysis using these random genotype data. Finally, we obtained the corrected permutation P-value of the meta-analysis by repeating the entire process N times. We used five real datasets and five simulation datasets to evaluate the MCPerm method and our results showed the following: (1) MCPerm requires only the summary statistics of the genotype, without the need for individual-level data; (2) Genotype counts generated by our two-step hypergeometric distributions had the same distributions as genotype counts generated by shuffling; (3) MCPerm had almost exactly the same permutation P-values as TradPerm (r = 0.999; P<2.2e-16); (4) The calculation speed of MCPerm is much faster than that of TradPerm. In summary, MCPerm appears to be a viable alternative to TradPerm, and we have developed it as a freely available R package at CRAN: http://cran.r-project.org/web/packages/MCPerm/index.html.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Lanying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Fanwu
authors.initials: F
authors.lastname: Kong
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lv
authors.affiliation: Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
mesh_terms: D006801:Humans; D030541:Databases, Genetic; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D009010:Monte Carlo Method; D009103:Multiple Sclerosis / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics; D012984:Software