Exact Conditional Efficiency Robust P-values from an Arbitrary Ranking of a Sample Space: an Application to Genome-wide Association Studied

Abstract

We introduce a general 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 Pr(P ≤α |H₀)≤α for all arameters under the null hypothesis and all significance levels α . 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.