Mendelian randomisation study of the associations of vitamin B12 and folate genetic risk scores with blood pressure and fasting serum lipid levels in three Danish population-based studies

Background/Objectives: The aim was to examine the association of genetic risk scores (GRSs) of vitamin B12 and folate-associated variants with blood pressure and lipids. Subjects/Methods: The study included 12 532 adults from three population-based studies (Inter99, Health2006 and Dan-MONICA10) conducted in Denmark. GRSs were calculated by summarising the number of vitamin B12 and folate increasing alleles. Weighted GRSs were calculated as the sum of weights for each allele corresponding to genetic effects sizes. Results: GRSs for serum vitamin B12 and folate were associated with serum vitamin B12 and folate, respectively. The β coefficients (95% confidence interval (CI), P- value) for regression of log-transformed serum B12/folate on the weighted GRSs were 0.57 (0.54, 0.61), P <0.001 and 0.85 (0.70, 1.01), P <0.01. No associations were observed between the vitamin B12 GRSs and any of the blood pressure and lipid-related outcomes in the combined analyses. Increasing number of folate increasing alleles was associated with increased high-density lipoprotein (HDL) cholesterol concentrations (β coefficient (95% CI, P -value) for regression of log-transformed HDL on the weighted GRSs, 0.081 (0.015, 0.148), P =0.017), but not with blood pressure, triglyceride, and low-density lipoprotein and total cholesterol levels. Conclusions: GRSs were not associated with blood pressure and lipid levels, except for an association between the GRS for folate and HDL cholesterol. Further studies are needed to determine whether a causal association between folate and HDL cholesterol exists.