Exact conditional efficiency robust P-values from an arbitrary ranking of a sample space: An application to genome-wide association studied

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 parameters 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.