Abstract
The causal interplay between thyroid dysfunction and gout remains controversial because of confounding and reverse causation in observational studies. Using Mendelian randomization (MR), this study investigated the causal effects of hyperthyroidism and hypothyroidism on the risk of gout. Summary statistics from the UK Biobank and FinnGen genome-wide association study databases were analyzed using 2-sample MR. Genetic instruments for thyroid dysfunction were selected under stringent criteria (P < 5 × 10-8, r2 < 0.001). Causal estimates were derived using inverse-variance weighted regression, supplemented by sensitivity analyses (MR-Egger, weighted median) and bidirectional MR. Genetically predicted hyperthyroidism exhibited a significant positive causal association with gout in both the UK Biobank (OR = 1.215, 95% confidence interval: 1.087-1.332, P = 3.12 × 10-5) and FinnGen cohorts (OR = 1.091, 95% confidence interval: 1.004-1.187, P = .041). No causal link was observed for the hypothyroidism. Bidirectional MR revealed no reverse causality, and sensitivity analyses confirmed robustness against pleiotropy and heterogeneity (P > .05). This study provides genetic evidence that hyperthyroidism is an independent risk factor of gout, indicating a possible unidirectional causal relationship. These findings underscore the necessity of closely monitoring uric acid levels in patients with hyperthyroidism and illuminating specific pathophysiological pathways that warrant further investigation of their underlying mechanisms.