Genetically predicted physical activity is associated with lower serum urate concentrations

Abstract

Background: Physical activity (PA) is considered to play an important role in the reduced gout risk. However, the epidemiology results are inconsistent and causality remains unclear.

Objective: To investigate the causal relationship of PA with serum urate concentrations and gout risk by a bidirectional Mendelian randomization (MR) approach.

Method: Two genome-wide association studies (GWASs) from UK Biobank were used to identify instrumental variables for self-reported moderate-to-vigorous PA (including 377,234 European individuals), accelerometer-measured 'average acceleration' PA (including 91,084 European individuals) and accelerometer-measured overall PA (including 91,105 European individuals). The summary data for serum urate (including 110,347 European individuals) and gout (including 2,115 cases and 67,259 controls) were derived from GWAS of Global Urate Genetics Consortium. Moreover, reverse direction Mendelian randomization study was conducted. The inverse-variance weighted, weighted median, Mendelian randomization Egger regression, simple mode and weighted mode and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were methods we performed.

Result: Genetic predisposition to accelerometer-measured 'average acceleration' PA [beta = -0.038; 95% confidence interval (CI) = -0.060,-0.015; P = 0.001] and accelerometer-measured overall PA (beta = -0.339; 95% CI = -0.522,-0.156; P = 2.8E-4) were significantly associated with decreased serum urate concentrations. Besides, there was no evidence supporting the causal association between PA and gout risk. In the reverse direction analysis, genetic predisposition to both urate and gout were not associated with PA being investigated.

Conclusions: In MR study, we found that PA may reduce serum urate concentrations but not the risk of gout. Moreover, serum urate concentrations and gout were not associated with PA.

Keywords: Gout; Mendelian randomization analysis; Physical activity; Serum urate.