The role of obesity, type 2 diabetes, and metabolic factors in gout: A Mendelian randomization study
Yang Yang, Wei Xian, Dide Wu, Zijun Huo, Shubin Hong, Yanbing Li, Haipeng Xiao
Abstract
Background: Several epidemiological studies have reported a possible correlation between risk of gout and metabolic disorders including type 2 diabetes, insulin resistance, obesity, dyslipidemia, and hypertension. However, it is unclear if this association is causal. Methods: We used Mendelian randomization (MR) to evaluate the causal relation between metabolic conditions and gout or serum urate concentration by inverse-variance-weighted (conventional) and weighted median methods. Furthermore, MR-Egger regression and MR-pleiotropy residual sum and outlier (PRESSO) method were used to explore pleiotropy. Genetic instruments for metabolic disorders and outcome (gout and serum urate) were obtained from several genome-wide association studies on individuals of mainly European ancestry. Results: Conventional MR analysis showed a robust causal association of increasing obesity measured by body mass index (BMI), high-density lipoprotein cholesterol (HDL), and systolic blood pressure (SBP) with risk of gout. A causal relationship between fasting insulin, BMI, HDL, triglycerides (TG), SBP, alanine aminotransferase (ALT), and serum urate was also observed. These results were consistent in weighted median method and MR-PRESSO after removing outliers identified. Our analysis also indicated that HDL and serum urate as well as gout have a bidirectional causal effect on each other. Conclusions: serum urate, as well as potential benefit of sound management of increased serum urate in patients with obesity, dyslipidemia, hypertension, and liver dysfunction.