Exact conditional p-values from arbitrary ranking of a sample space: An application to genome-wide association studies

Abstract

We introduce a method for computation of exact conditional efficiency robust enumeration p-values for detection of genotype--phenotype associations at a single bi-allelic genetic locus. Our method can be based on any arbitrary ranking test statistics, such as efficiency robust test statistics or asymptotic p-values. The resulting p-values are exact conditional enumeration p-values and satisfy the basic statistical validity property. Practically, the method allows performing statistically valid significance testing in genomic analyses with unknown modes of inheritance at individual bi-allelic genetic loci -- the situation typical in genome-wide association studies. We provide an open-source R code implementing the method.