Leveraging pleiotropic clustering to address high proportion correlated horizontal pleiotropy in Mendelian randomization studies.

ABSTRACT: Mendelian randomization harnesses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. However, certain genetic variants can affect both the exposure and the outcome through a shared factor. This phenomenon, called correlated horizontal pleiotropy, may result in false-positive causal findings. Here, we propose a Pleiotropic Clustering framework for Mendelian randomization, PCMR. PCMR detects correlated horizontal pleiotropy and extends the zero modal pleiotropy assumption to enhance causal inference in trait pairs with correlated horizontal pleiotropic variants. Simulations show that PCMR can effectively detect correlated horizontal pleiotropy and avoid false positives in the presence of correlated horizontal pleiotropic variants, even wh

SUBMITTER: Tang B 

PROVIDER: S-EPMC11928562 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature