Marginal screening of 2 × 2 tables in large-scale case-control studies.

Assessing the statistical significance of risk factors when screening large numbers of 2×2 tables that cross-classify disease status with each type of exposure poses a challenging multiple testing problem. The problem is especially acute in large-scale genomic case-control studies. We develop a potentially more powerful and computationally efficient approach (compared with existing methods, including Bonferroni and permutation testing) by taking into account the presence of complex dependencies between the 2×2 tables. Our approach gains its power by exploiting Monte Carlo simulation from the estimated null distribution of a maximally selected log-odds ratio. We apply the method to case-control data from a study of a large collection of genetic variants related to the risk of early onset stroke.