The causal associations of circulating amino acids with blood pressure: a Mendelian randomization study

Circulating levels of amino acids were associated with blood pressure (BP) in observational studies. However, the causation of such associations has been hypothesized but is difficult to prove in human studies. Here, we aimed to use two-sample Mendelian randomization analyses to evaluate the potential causal associations of circulating levels of amino acids with BP and risk of hypertension. We generated genetic instruments for circulating levels of nine amino acids by conducting meta-analyses of genome-wide association study (GWAS) in UK Biobank participants with metabolomic data (n = 98,317) and another published metabolomics GWAS (n = 24,925). Data on the associations of the genetic variants with BP and hypertension were obtained in the UK Biobank participants without metabolomic data (n = 286,390). The causal effects were estimated using inverse-variance weighted method. Significant evidence consistently supported the causal effects of increased branched-chain amino acids (BCAAs, i.e., leucine, isoleucine, and valine) levels on higher BP and risk of hypertension (all P