Liability of gout has a causal effect on the onset of hypertension, but liability of hypertension does not have a causal effect on the onset of gout, according to the results of a Mendelian randomization (MR) study published in Arthritis Research & Therapy.
Because of limited evidence, the researchers of the current study sought to evaluate the causal relationships between gout and hypertension.
Genetic information was collected from the Taiwan Biobank, which included a total of 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel MR model with coarsened exposures was used to explore the causality between the liability of gout on hypertension and the liability of hypertension on gout. Overall, 4 SNPs associated with gout and 10 SNPs associated with hypertension were included, following the removal of any SNPs considered to be associated with measured confounders.
Inverse-variance weighted (IVW) and polygenic risk score (PRC) procedures were used to estimate the causal effect size. The MR analysis with coarsened exposures was conducted with and without adjustments for covariates.
Among the 88,347 study participants, 3.68% (n=3253) had gout and 13.52% (n=11,948) had hypertension. Overall, 31.9% of the participants were men. The mean participant age was 51.1 (SD, 11.1) years.
Results of the study showed that following adjustments for measured confounders, MR analysis with coarsened exposures demonstrated a significant positive causal effect of the liability of gout on hypertension with both the IVW method (relative risk [RR], 1.10; 95% CI, 1.03-1.19; P =.0077) and the PRS method (RR, 1.10; 95% CI, 1.02-1.19;
P =.0092). The result of causality reported was the same both before and after the involvement of measured confounders.
However, no causal effect of liability of hypertension on gout was observed.
Limitations of the current study should be noted. Even though MR analysis with coarsened exposures included SNPs with pleiotropic effects to increase efficiency of the estimates, the incorrect classification of pleiotropic SNPs as valid instrumental variables may have introduced biased results. In addition, the Taiwanese population may have different epidemiologic or genetic features for gout and hypertension compared with other Asian populations.
The study authors concluded that “…it may be beneficial for clinicians to view gout as a chronic disease with important systemic effects rather than simply acute self-limiting arthritis.”
Lai B, Yu HP, Chang YJ, et al. Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures. Arthritis Res Ther. 2022;24(1):243. doi:10.1186/s13075-022-02933-4