Genetically Predict Diet‐derived Antioxidants and Risk of Neurodegenerative Diseases Among Individuals of European Descent: A Mendelian Randomization Study

作者：Qing‐Qing Duan, Wei‐Ming Su, Xiaojing Gu, Jiang Long, Zheng Jiang, Kang‐Fu Yin, Wei‐Chen Cai, Bei Cao, Li‐Yi Chi, Xia Gao, Ju-Rong Li, Yong‐Ping Chen · 发表于：Brain and Behavior · 年份：2025 · DOI：10.1002/brb3.70766 · 被引用次数：3 · 研究领域：Amyotrophic Lateral Sclerosis Research、Genomics, phytochemicals, and oxidative stress、Parkinson's Disease Mechanisms and Treatments

BACKGROUND: The incidence of neurodegenerative disorders (NDDs) is increasing, and currently, there are no curative treatments available for these conditions. The potential benefits of supplementation with diet-derived antioxidants and their metabolites for NDDs remain a subject of debate. In this study, we employed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between elevated circulating antioxidant levels and the risk of NDDs. METHODS: We used single-nucleotide polymorphisms (SNPs) related to diet-derived antioxidants and p < 1E-05 as instrumental variables (IVs). The NDDs we studied included Parkinson's disease (PD) (33,674 cases and 449,056 controls), Alzeimers disease (AD) (111,326 cases and 677,663 controls), amyotrophic lateral sclerosis (ALS) (27,205 cases and 110,881 controls), and frontotemporal dementia (FTD) (3526 cases and 9402 controls) from GWASs conducted in the European descent. Two-sample MR was performed together with a series of sensitivity analyses. The main statistical analyses were conducted using the package "TwoSampleMR (V.0.5.6)" in R (V.4.2.0). RESULTS: Genetically predicted levels of α-tocopherol and carotene were found to be associated with a reduced risk of ALS, with odds ratios (OR) of 0.45 (95% confidence interval [CI]: 0.31, 0.66; p = 3.97 × 10^-5) and 0.82 (95% CI: 0.68, 0.99; p = 0.0427), respectively. Similarly, vitamin E (OR 0.70; [95% CI 0.50, 0.98]; p = 0.0358) and ascorbate (OR 0.85...