A novel multivariable Mendelian randomization framework to disentangle highly correlated exposures with application to metabolomics.

ABSTRACT: Mendelian randomization (MR) utilizes genome-wide association study (GWAS) summary data to infer causal relationships between exposures and outcomes, offering a valuable tool for identifying disease risk factors. Multivariable MR (MVMR) estimates the direct effects of multiple exposures on an outcome. This study tackles the issue of highly correlated exposures commonly observed in metabolomic data, a situation where existing MVMR methods often face reduced statistical power due to multicollinearity. We propose a robust extension of the MVMR framework that leverages constrained maximum likelihood (cML) and employs a Bayesian approach for identifying independent clusters of exposure signals. Applying our method to the UK Biobank metabolomic data for the largest Alzheimer disease (AD) cohort

SUBMITTER: Chan LS 

PROVIDER: S-EPMC11393695 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature