Analysis of rare variant population structure in Europeans explains differential stratification of gene-based tests.

ABSTRACT: There is substantial interest in the role of rare genetic variants in the etiology of complex human diseases. Several gene-based tests have been developed to simultaneously analyze multiple rare variants for association with phenotypic traits. The tests can largely be partitioned into two classes - 'burden' tests and 'joint' tests - based on how they accumulate evidence of association across sites. We used the empirical joint site frequency spectra of rare, nonsynonymous variation from a large multi-population sequencing study to explore the effect of realistic rare variant population structure on gene-based tests. We observed an important difference between the two test classes: their susceptibility to population stratification. Focusing on European samples, we found that joint tests, whi

SUBMITTER: Zawistowski M 

PROVIDER: S-EPMC4135410 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature