Circulating Concentrations of Nutrition-Related Factors Are Not Causally Associated With Atrial Fibrillation: A Mendelian Randomization Study

Observational studies reported conflicting results regarding the association between circulating concentrations of nutrition-related factors and atrial fibrillation (AF). The aim of this study was to evaluate the potential causal effect of 8 circulating nutrition-related factors (vitamin B12, vitamin E, folate, retinol, β-carotene, iron, zinc, and copper) on AF risk using mendelian randomization (MR). Summary-level data for the nutrition-related factors and AF were obtained from genome-wide association studies conducted among individuals of European ancestry. The genome-wide association study on AF included 60,620 cases and 970,216 controls. A 2-sample MR design was applied for evaluating the causal association. In the primary MR analyses, the inverse variance-weighted method did not identify any causal effect of circulating concentrations of vitamin B12 [β = 0.000, standard error (SE) = 0.021, P = 0.994], vitamin E (β = 0.080, SE = 0.152, P = 0.600), retinol (β = 0.098, SE = 0.397, P = 0.806), folate (β = -0.006, SE = 0.052, P = 0.901), β-carotene (β = 0.014, SE = 0.025, P = 0.560), iron (β = -0.009, SE = 0.072, P = 0.905), zinc (β = 0.038, SE = 0.032, P = 0.239), and copper (β = -0.012, SE = 0.023, P = 0.589) on AF. The MR-Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) analyses did not suggest the presence of pleiotropy. In addition, the lack of association remained in the leave-one-out analysis. This MR study indicates no causal association of circulating concentrations of vitamin B12, vitamin E, folate, retinol, β-carotene, iron, zinc, and copper with AF.