A unified mixed-effects model for rare-variant association in sequencing studies.

ABSTRACT: For rare-variant association analysis, due to extreme low frequencies of these variants, it is necessary to aggregate them by a prior set (e.g., genes and pathways) in order to achieve adequate power. In this paper, we consider hierarchical models to relate a set of rare variants to phenotype by modeling the effects of variants as a function of variant characteristics while allowing for variant-specific effect (heterogeneity). We derive a set of two score statistics, testing the group effect by variant characteristics and the heterogeneity effect. We make a novel modification to these score statistics so that they are independent under the null hypothesis and their asymptotic distributions can be derived. As a result, the computational burden is greatly reduced compared with permutation-ba

SUBMITTER: Sun J 

PROVIDER: S-EPMC3740585 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature