Causal relationship between plasma metabolites and hypertension: A Mendelian randomization study

Abstract

Observational studies have indicated an association between metabolites and hypertension. However, establishing a causal relationship remains challenging. This study aims to investigate this causal relationship using Mendelian randomization methodology. Genome-wide association study summary statistics for plasma metabolites were obtained from 3 studies, encompassing over 2000 varieties. Genome-wide association study summary statistics for hypertension were derived from 2 studies, with a sample size of 122,996 and 129,909, respectively. The main method used was the inverse variance weighting (IVW) method, and the results were adjusted using Bonferroni multiple correction. The IVW method estimated effects between the levels of taurochenodeoxycholate, 1-dihomo-linolenoyl-GPC (20:3n3 or 6), N-acetylphenylalanine, and dihomo-linolenate (20:3n3 or n6) and hypertension are 1.041 (95% confidence interval [CI] 1.022-1.059, P = 1.49e-05), 1.023 (95% CI 1.015-1.031, P = 5.32e-08), 1.029 (95% CI 1.021-1.037, P = 6.10e-12), and 1.019 (95% CI 1.010-1.028, P = 1.54e-05), respectively. The IVW method estimated effects between the levels of 2-hydroxyoctanoate, 1-docosapentaenoyl-GPC (22:5n3), X-11538, gamma-glutamyl-alpha-lysine, and 2-butenoylglycine and hypertension are 0.954 (95% CI 0.936-0.972, P = 8.87e-07), 0.981 (95% CI 0.973-0.989, P = 4.14e-06), 0.981 (95% CI 0.975-0.987, P = 7.53e-10), 0.942 (95% CI 0.922-0.963, P = 8.71e-08), and 0.930 (95% CI 0.902-0.958, P = 2.22e-06), respectively. In summary, there are indications that some metabolites have a causal relationship with hypertension. It is necessary to conduct further investigations to comprehend the underlying biological mechanisms that support these associations.

Keywords: Mendelian randomization; causal effect; hypertension; plasma metabolites.