Exploring the causal relationship between dietary macronutrients and neurodegenerative diseases: a bi-directional two-sample Mendelian randomization study

Aim: The associations between dietary macronutrient intake and neurodegenerative diseases (NDDs) have been widely reported; however, the causal effect remains unclear. current study aimed to estimate relationship (i.e., carbohydrate, fat, protein) NDDs [e.g., Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS)]. Methods: Mendelian randomization (MR) was applied evaluate NDDs. We used single-nucleotide polymorphisms strongly associated (P < 5 × 10-8) with exposures from genome-wide association studies as instrumental variables. Inverse-variance weighted, MR-Egger, weighted median, MR pleiotropy residual sum outlier were verify assumptions. Results: Genetically predicted higher carbohydrate an increased risk of ALS [odds ratio (OR), 2.741, 95% confidence interval (CI): 1.419-5.293, P = 0.003). Vulnerability PD negatively relative fat (OR, 0.976, 95%CI: 0.959-0.994, 0.012) protein 0.987, 0.975-1.000, 0.042). also identified influence AD on 1.022, 1.011-1.034, 0.001). Conclusion: found solid evidence supporting idea that a proportion causally increases risk. is intake. may decrease in fat.