Association between human blood metabolome and the risk of hypertension

Abstract

Hypertension, commonly referred to as high blood pressure, is a chronic medical condition characterized by persistently elevated blood pressure levels. It is a prevalent global health issue, affecting a significant portion of the population worldwide. Hypertension is often asymptomatic, making it a silent but potentially dangerous condition if left untreated. Genetic instruments for 1,091 were from a recent comprehensive metabolome genome-wide association study (GWAS). Summary statistics of diastolic blood pressure (DBP) and systolic blood pressure (SBP) involving 757,601 sample size were analyzed. Two-sample Mendelian Randomization (MR) was conducted to assess causal effect of metabolites on DBP and SBP risk, and reverse MR analysis was performed to identify the DBP/SBP causal effect on blood metabolites. Twelve and twenty-two metabolites were identified to be associated with DBP and SBP, respectively. Sensitive analysis showed four metabolites had robustness association on BP. Reverse MR demonstrated DBP and SBP could decrease the tricosanoyl sphingomyelin (d18:1/23:0)* level and increase the 2-hydroxyhippurate (salicylurate) level in blood, respectively. Our findings reveal an association between blood metabolites and blood pressure (DBP and SBP), suggesting potential therapeutic targets for hypertension intervention.

Keywords: Diastolic blood pressure; Hypertension; Mendelian randomization; Systolic blood pressure.

Fig. 1

Overview of this MR study

Fig. 2

Blood metabolites associations for hypertension. (A) Volcano plot demonstrating negative (blue) and positive (red) blood metabolites associations with DBP; points are colored where P < 0.05/707. (B) Volcano plot demonstrating negative (blue) and positive (red) blood metabolites associations with SBP; points are colored where P < 0.05/703

Fig. 3

Bidirectional Mendelian randomization analysis supports causal associations for blood metabolites on hypertension and vice versa. (A) Comparison of bidirectional two-sample MR -log₁₀ (p-values) for the 707 metabolites that could be investigated in both directions, where the x-axis indicates the p-value for a causal effect of blood metabolites on DBP and the y-axis indicates the p-value for a causal effect of DBP on blood metabolites. (B) Comparison of bidirectional two-sample MR -log₁₀ (p-values) for the 703 metabolites that could be investigated in both directions, where the x-axis indicates the p-value for a causal effect of blood metabolites on SBP and the y-axis indicates the p-value for a causal effect of SBP on blood metabolites. Significant metabolites as indicated in the legend, while the dashed lines indicate significant threshold after Bonferroni correction