Appraising the Role of Circulating Concentrations of Micronutrients in Hypertension: A Two-sample, Multivariable Mendelian Randomization Study

Abstract

Background: Hypertension poses a significant global health challenge, warranting exploration of novel preventive measures. This study aimed to investigate the role of circulating concentrations of various micronutrients in hypertension using a Mendelian randomization (MR) approach. Methods: Data on hypertension were obtained from FinnGen, comprising 55,917 cases and 162,837 controls of European ancestry. Fifteen micronutrients were evaluated and selected based on genome-wide association studies (GWAS) data. Instrumental single nucleotide polymorphisms (SNPs) were chosen according to strict criteria. Univariable Mendelian randomization (UVMR) analysis was conducted using the inverse variance weighted (IVW) method, supplemented by sensitivity analyses. Multivariate Mendelian randomization (MVMR) analysis was performed to assess interactions between micronutrients. Results: In UVMR analysis, the IVW method revealed a potential influence of copper (OR = 1.052, 95% CI: 1.006–1.099, P = 0.025) and zinc (OR = 1.083, 95% CI: 1.007–1.165, P = 0.031) on hypertension. Sensitivity analyses supported these findings. MVMR analysis confirmed a direct positive effect of zinc on hypertension (OR = 1.087, 95% CI: 1.026–1.151, P = 0.005), while adjusting for zinc attenuated the effect of copper on hypertension (OR = 1.026, 95% CI: 0.987–1.066, P = 0.193). Conclusion: Circulating zinc levels may be a potential risk factor for hypertension, while the association with other micronutrients remains inconclusive. These findings suggest that reducing zinc intake within a healthy range may help lower hypertension risk. Future research should further explore the role of zinc and nonlinear associations for a more comprehensive understanding.