Genetic homocysteine risk shapes cardiocerebral structure and multimorbidity through age- and sex-specific mechanisms: a UK Biobank study.

ABSTRACT:

Background

Elevated homocysteine (Hcy) levels have been implicated in cardiometabolic and neurological disorders. However, the age- and sex-specific mechanisms by which genetically determined Hcy levels contribute to disease risk via structural alterations in the heart and brain remain unclear.

Methods

We analyzed data from 306,796 UK Biobank participants. A weighted polygenic risk score (PRS) for Hcy was constructed and tested for associations with cardiovascular and neuroimaging phenotypes. Mediation analyses assessed the extent to which these structural traits mediated disease risk. We also examined whether two dietary patterns-the sulfur microbial diet and the EAT-Lancet diet-modulated Hcy levels or disease associations.

Results

Genetically elevated Hcy was signif

SUBMITTER: Feng C 

PROVIDER: S-EPMC12661569 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature