Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian randomization approaches.

ABSTRACT:

Background

Mendelian randomization (MR) leverages trait associated genetic variants as instrumental variables (IVs) to determine causal relationships in epidemiology. However, genetic IVs for complex traits are typically highly heterogeneous and, at a molecular level, exert effects on different biological processes. Exploration of the biological underpinnings of such heterogeneity can enhance our understanding of disease mechanisms and inform therapeutic strategies. Here, we introduce a new approach to instrument partitioning based on enrichment of Mendelian disease categories (pathway-partitioned) and compare it to an existing method based on genetic colocalization in contrasting tissues (tissue-partitioned).

Methods

We employed individual- and summary-level MR methodologie

SUBMITTER: Leyden GM 

PROVIDER: S-EPMC12079859 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature