Causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures

Objectives: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to determine the causal relationship between gout and hypertension. Methods: We obtained genetic information from the Taiwan Biobank including 88347 participants and 686439 single nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between liability of gout on hypertension and vice versa using 9 SNPs associated with gout and 16 SNPs associated with hypertension. The binary exposure (gout/hypertension) was visualized as a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The analysis was performed with and without adjustments for covariates. Results: Of the 88,347 participants, 3,253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). In unadjusted models, MR analysis showed significant positive causal effect of gout on hypertension in both the IVW method (relative risk [RR], 1.12; 95% confidence interval [CI], 1.05–1.20; p = 4 ´ 10 -4 ) and the PRS method (RR, 1.12; 95% CI, 1.03–1.21; p = 0.0063). The direction and effect size were similar before and after covariate adjustment. The causal effect of hypertension on gout was not statistically significant. Conclusions: In this study, we showed that gout has a causal effect on hypertension, but hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension.