The causal role of homocysteine in multiple diseases: a systematic review of Mendelian randomization studies

作者：Xiuyuan Zhu, Jiangnan Wei, Jingling Li, Shunli Zuo, Jiaxian Wang, Ning Liu · 发表于：Nutrition & Metabolism · 年份：2025 · DOI：10.1186/s12986-025-00933-0 · 被引用次数：9 · 研究领域：Folate and B Vitamins Research、Genetic Associations and Epidemiology、Nutrition and Health in Aging

BACKGROUND: Homocysteine (Hcy) has been implicated in the development of multiple diseases; however, its causal role remains unclear. Mendelian randomization (MR) studies provide a robust approach to assessing causality by minimizing confounding and reverse causation. OBJECTIVE: This study aimed to evaluate the causal role of Hcy in various diseases by synthesizing evidence from MR studies. METHODS: We performed a comprehensive literature search in PubMed, the Cochrane Library, Embase, and Web of Science for MR studies published up to May 30, 2024. Studies investigating the association between genetic predisposition to Hcy levels and specific diseases were included. RESULTS: Findings from 33 MR studies (covering 31 distinct primary outcomes) suggest that genetically elevated Hcy levels are associated with an increased risk of several health conditions, including: Five cardiovascular diseases: small vessel stroke, small artery occlusion stroke, stroke, subarachnoid hemorrhage, and ischemic stroke. Six musculoskeletal diseases: soft tissue disorders, osteoporosis with pathological fractures, hospital-diagnosed osteoarthritis (OA), overall OA, knee OA, and hip OA. One musculoskeletal biomarker: waist-to-hip ratio (WHR) adjusted for BMI. Two digestive system diseases: gastric cancer and non-alcoholic fatty liver disease. Three digestive biomarkers: alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). One urogenital system disease: chro...