Joint association testing of common and rare genetic variants using hierarchical modeling.

ABSTRACT: New sequencing technologies provide an opportunity for assessing the impact of rare and common variants on complex diseases. Several methods have been developed for evaluating rare variants, many of which use weighted collapsing to combine rare variants. Some approaches require arbitrary frequency thresholds below which to collapse alleles, and most assume that effect sizes for each collapsed variant are either the same or a function of minor allele frequency. Some methods also further assume that all rare variants are deleterious rather than protective. We expect that such assumptions will not hold in general, and as a result performance of these tests will be adversely affected. We propose a hierarchical model, implemented in the new program CHARM, to detect the joint signal from rare an

SUBMITTER: Cardin NJ 

PROVIDER: S-EPMC4339046 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature