COMBAT {COMBAT}

A Combined Gene-based Association Test

Description

This function implements a combined gene-based association test using SNP-level P values and reference genotype data.

Usage

COMBAT(x, snp.ref, vegas.pct = c(0.1,0.2,0.3,0.4,1), pca_cut_perc = 0.995,
   nperm = 100, seed=12345, ncores=1)

Arguments

x

a vector of SNP-level P values.

snp.ref

a matrix of SNP genotypes (coded as allele counts) from reference samples, with samples in rows and SNPs in columns.

vegas.pct

a numeric vector, fraction of the top SNPs to be used in the VEGAS method.

pca_cut_perc

numeric, cutoff for percentage of sum of eigen values in the simpleM approach.

nperm

number of permutations for computing the correlation between P values of different tests.

seed

random seed to derive consistent outcome.

ncores

number of CPU cores for parallel computing.

Details

COMBAT uses simulation and the extended Simes procedure (ext_simes) to combine multiple gene-based association test statistics (currently including gates, vegas, and simpleM) to perform a more powerful association analysis. This method does not require raw genotype or phenotype data, but needs only SNP-level P-values and correlations between SNPs from ancestry-matched samples. The technical details about the method is described in Wang et al (2017) <doi:10.1534/genetics.117.300257>.

Value

A vector of p-values from COMAT and each individual gene-based test.

References

Minghui Wang, Jianfei Huang, Yiyuan Liu, Li Ma, James B. Potash, Shizhong Han. COMBAT: A Combined Association Test for Genes using Summary Statistics. Genetics 2017, 207(3): 883-891. https://doi.org/10.1534/genetics.117.300257.

See Also

ext_simes, gates, vegas, simpleM.

Examples

# read SNP P values
file1 <- paste(path.package("COMBAT"),"extdata","SNP_info.txt.gz",sep="/")
snp.info  <- read.table(file1, header = TRUE, as.is=TRUE)
snp.pvals <- as.matrix(snp.info[,2])

# read reference genotype
file2 <- paste(path.package("COMBAT"),"extdata","SNP_ref.txt.gz",sep="/")
snp.ref   <- read.table(file2, header = TRUE)
snp.ref   <- as.matrix(snp.ref)
#call COMBAT

COMBAT(snp.pvals, snp.ref, nperm=100, ncores=2)