Dietary One‑Carbon Nutrients and Genetic Risk in Parkinson’s Disease: A Prospective Cohort Study

Abstract Background Several studies have investigated the effects of dietary one-carbon metabolism (OCM) nutrients, such as methionine, folate, vitamin B6, and vitamin B12, on Parkinson’s disease (PD). However, current evidence remains insufficient to definitively establish a link between OCM intake, PD incidence, and genetic risk. Methods Among 202171 individuals aged 37-73 in the UK Biobank, we assessed dietary OCM nutrient intake via repeated 24‑hour recalls, determined PD incidence via validated ICD‑10 codes, and quantified genetic risk with polygenic risk scores. Employing Cox proportional hazards models supplemented by sensitivity analyses, we evaluated the associations and potential interactions among OCM nutrient intake, genetic risk, and PD incidence. Results Over a median 12.27-year follow-up of 202171 participants, 1037 incident PD cases occurred. In multivariable-adjusted Cox models, compared with participants in the lowest quartile, those in the highest quartile of methionine, vitamin B6, folate, and vitamin B12 had a lower risk of PD HR (95% CI)=0.83 (0.69–1.00), 0.75 (0.62–0.90), 0.71 (0.59–0.85), and 0.79 (0.65–0.94). Genetically-stratified analyses showed folate inversely associated with PD risk in the low-risk group HR (95% CI)= 0.65 (0.48–0.88) (P for interaction = 0.48); vitamin B12 linked to lower risk in the high-risk group HR (95% CI)= 0.78 (0.63–0.99) (P for interaction = 0.83); and vitamin B6 inversely associated across both strata high-risk HR (95% CI)= 0.77 (0.62–0.97); low-risk HR (95% CI) = 0.59 (0.44–0.80)(P for interaction = 0.08). Conclusions Higher OCM nutrient intake might be inversely associated with PD risk. However, evidence regarding the independent contributions of dietary and genetic factors remains inconclusive.