Generalized multi-SNP mediation intersection-union test.

ABSTRACT: To elucidate the molecular mechanisms underlying genetic variants identified from genome-wide association studies (GWAS) for a variety of phenotypic traits encompassing binary, continuous, count, and survival outcomes, we propose a novel and flexible method to test for mediation that can simultaneously accommodate multiple genetic variants and different types of outcome variables. Specifically, we employ the intersection-union test approach combined with the likelihood ratio test to detect mediation effect of multiple genetic variants via some mediator (e.g., the expression of a neighboring gene) on outcome. We fit high-dimensional generalized linear mixed models under the mediation framework, separately under the null and alternative hypothesis. We leverage Laplace approximation to comput

SUBMITTER: Zhong W 

PROVIDER: S-EPMC8986032 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature