Genetically predict diet-derived Antioxidants and risk of Neurodegenerative diseases among individuals of European descent: a Mendelian randomization study

Abstract

Abstract Background The prevalence of neurodegenerative disorders (NDDs) is increasing, and there is no cure for any of these diseases. Antioxidants have been associated with several diseases in observational studies. However, the relationship between antioxidants and neurodegenerative diseases remains unclear. The purpose of this study is to use publicly available genome-wide association studies (GWAS) summary statistics to examine the causal relationship between diet-derived antioxidants and the risk of NDDs. Methods Single-nucleotide polymorphisms associated with diet-derived antioxidants (vitamin A, vitamin B6, vitamin C, vitamin E, carotene, β-carotene, lycopene, zinc, and selenium) and their metabolites (α-tocopherol, γ-tocopherol, ascorbate, and retinol) were employed as instrumental variables. The NDDs we studied included Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), which were obtained from GWASs conducted in the European population. Two-sample Mendelian randomization (MR) was performed together with a series of sensitivity analyses. The main statistical analyses were conducted using package “TwoSampleMR (V.0.5.6)” in R (V.4.2.0) Results Genetically predicted α-tocopherol led to a lower risk of ALS (OR 0.45; 95% CI, 0.31, 0.66; p = 3.97E-05) based on the random-effect IVW method, and no evidence of heterogeneity and horizontal pleiotropy was found. In addition, we found a potential protective effect of vitamin E and ascorbate on PD, carotene on ALS, and retinol on FTD. However, no circulating antioxidants studied affect the risk for AD. Conclusion This study indicated that some diet-derived antioxidants or their metabolites showed evidence of causality in NDDs and provided promising targets for therapeutics.