Assessing the Causal Effects of Adipokines on Uric Acid and Gout: A Two-Sample Mendelian Randomization Study
Ruyi Cong, Xiaoyu Zhang, Zihong Song, Shanshan Chen, Guanhua Liu, Yizhi Liu, Xiuyu Pang, Fang Dong, Weijia Xing, Youxin Wang, Xizhu Xu
Abstract
Previous observational studies have highlighted associations between adipokines and hyperuricemia, as well as gout, but the causality and direction of these associations are not clear. Therefore, we attempted to assess whether there are causal effects of specific adipokines (such as adiponectin (ADP) and soluble leptin receptors (sOB-R)) on uric acid (UA) or gout in a two-sample Mendelian randomization (MR) analysis, based on summary statistics from large genome-wide association studies. The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (including MR-Egger regression, weighted median, penalized weighted median, and MR pleiotropy residual sum and outlier methods) were also performed, to ensure reliable results. In the IVW models, no causal effect was found for sOB-R (odds ratios (OR), 1.002; 95% confidence intervals (CI), 0.999–1.004; p = 0.274) on UA, or ADP (OR, 1.198; 95% CI, 0.865–1.659; p = 0.277) or sOB-R (OR, 0.988; 95% CI, 0.940–1.037; p = 0.616) on gout. The results were confirmed in sensitivity analyses. There was no notable directional pleiotropy or heterogeneity. This study suggests that these specific adipokines may not play causal roles in UA or gout development.