MPGE {MPGE}

MPGE: an R package to implement a two-step approach to testing overall effect of gene-environment interaction for multiple phenotypes.

Description

Interaction between a genetic variant (e.g., a SNP) and an environmental variable (e.g., physical activity) can have a shared effect on multiple phenotypes (e.g., LDL and HDL). MPGE is a two-step method to test for an overall interaction effect on multiple phenotypes. In first step, the method tests for an overall marginal genetic association between the genetic variant and the multivariate phenotype. In the second step, SNPs which show an evidence of marginal overall genetic effect in the first step are prioritized while testing for an overall GxE effect. That is, a more liberal threshold of significance level is considered in the second step while testing for an overall GxE effect for these promising SNPs compared to the other SNPs.

Details

The package consists of following functions: mv_G_GE, WHT; SST.

Functions

mv_G_GE

for a batch of genetic variants, this function provides two different p-values for each genetic variant, one from the test of marginal overall genetic association with multiple phenotypes , and the other from the test of overall GxE effect on multivariate phenotype allowing for a possible marginal effect due to the genetic variant and a marginal effect due to the environmental variable.

WHT

this function implements the weighted multiple hypothesis testing procedure to adjust for multiple testing while combining the two steps of testing gene-environment interaction in the two-step GxE testing procedure, given two sets of p-values obtained using the previous function mv_G_GE for genome-wide genetic variants.

SST

this function implements the subset multiple hypothesis testing procedure to adjust for multiple testing while combining the two steps of testing gene-environment interaction based on the same two sets of p-values described above.

References

A Majumdar, KS Burch, S Sankararaman, B Pasaniuc, WJ Gauderman, JS Witte (2020) A two-step approach to testing overall effect of gene-environment interaction for multiple phenotypes. bioRxiv, doi: https://doi.org/10.1101/2020.07.06.190256