ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutritional Epidemiology
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1637592
This article is part of the Research TopicThe Impact of Dietary Patterns and Nutrients on Cardiometabolic DiseasesView all 5 articles
Genetic homocysteine risk shapes cardiocerebral structure and multimorbidity through age-and sex-specific mechanisms: a UK Biobank study
Provisionally accepted
- Ningxia Medical College, Yinchuan, China
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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 significantly associated with sex-and age-specific alterations in brain white matter and cardiac structure. These structural traits partially mediated the link between Hcy and hypertension, dyslipidemia, and cognitive impairment. Surprisingly, neither dietary index was associated with Hcy levels, although both showed independent associations with disease risk. Conclusion: Our findings suggest that genetically determined Hcy levels impact cardiocerebral structure in a sex-and age-dependent manner, contributing to disease risk. Structural imaging phenotypes offer potential as early mediators. The dietary effects on disease risk may involve pathways independent of Hcy modulation.
Keywords: Homocysteine, sulfur microbial diet, eat-lancet, CardiovascularStructure, Cardiocerebrovascular diseases, UK Biobank
Received: 29 May 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Feng, Ma, Zhang, Zhao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
YU Zhao, zhaoyu@nxmu.edu.cn
Peng Zhang, pengz@nxmu.edu.cn
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