VTCMC assumes the same direction of effect for all rare variants within a gene. It sums the number of observed rare alleles within the gene for each person, and tests the association between the gene-based sumscore and the phenotype. Since the optimal MAF cutoff for “rare” variants is unknown, the VTCMC uses the cutoff that yields the strongest effect. Since the SNP effects and the MAF cutoff are chosen in the same data, the resulting p-value is asymptotically corrected for capitalization on chance.
