A robust two-sample transcriptome-wide Mendelian randomization method integrating GWAS with multi-tissue eQTL summary statistics.

ABSTRACT: By treating genetic variants as instrumental variables (IVs), two-sample Mendelian randomization (MR) methods detect genetically regulated risk exposures for complex diseases using only summary statistics. When considering gene expression as exposure in transcriptome-wide MR (TWMR) analyses, the eQTLs (expression-quantitative-trait-loci) may have pleiotropic effects or be correlated with variants that have effects on disease not via expression, and the presence of those invalid IVs would lead to biased inference. Moreover, the number of eQTLs as IVs for a gene is generally limited, making the detection of invalid IVs challenging. We propose a method, "MR-MtRobin," for accurate TWMR inference in the presence of invalid IVs. By leveraging multi-tissue eQTL data in a mixed model, the proposed

SUBMITTER: Gleason KJ 

PROVIDER: S-EPMC9027205 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature