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

TL;DR

This paper presents a method to compute exact conditional p-values for genotype-phenotype association tests in genome-wide studies, accommodating arbitrary ranking statistics and ensuring statistical validity.

Contribution

The authors introduce a novel method for calculating exact conditional p-values applicable to any ranking test statistic in genome-wide association studies.

Findings

Provides exact p-values for genotype-phenotype associations

Applicable to arbitrary ranking test statistics

Enables valid significance testing in complex genetic analyses

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.