Bootstrat: Population Informed Bootstrapping for Rare Variant Tests

Recent advances in genotyping and sequencing technologies have made detecting rare variants in large cohorts possible. Various analytic methods for associating disease to rare variants have been proposed, including burden tests, C-alpha and SKAT. Most of these methods, however, assume that samples come from a homogeneous population, which is not realistic for analyses of large samples. Not correcting for population stratification causes inflated p-values and false-positive associations. Here we propose a population-informed bootstrap resampling method that controls for population stratification (Bootstrat) in rare variant tests. In essence, the Bootstrat procedure uses genetic distance to cr