Do Serum Urate–Associated Genetic Variants Differentially Contribute to Gout Risk According to Body Mass Index? Analysis of the UK Biobank

Abstract

Objective: To examine whether urate-associated genetic variants differ in their influence on gout risk according to body mass index (BMI). Methods: This research was conducted using the UK Biobank Resource (n = 358,728). Participants were divided into 3 groups: BMI <25 kg/m2 (low/normal), BMI ≥25 kg/m2–<30 kg/m2 (overweight), and BMI ≥30 kg/m2 (obese). Gene–BMI interactions for gout association were tested by logistic regression using a urate genetic risk score (GRS). Results: Compared to participants with a GRS less than the mean, the prevalence of gout was higher in those with a GRS greater than or equal to the mean in the low/normal BMI group (0.27% versus 0.77%), in the overweight BMI group (1.02% versus 3.02%), and in the obese BMI group (2.49% versus 6.23%). A GRS greater than or equal to the mean was positively associated with gout compared to a GRS less than the mean in the low/normal BMI group (odds ratio [OR] 2.89 [95% confidence interval (95% CI) 2.42–3.47]), in the overweight BMI group (OR 3.09 [95% CI 2.84–3.36]), and in the obese BMI group (OR 2.65 [95% CI 2.46–2.86]). There was a mildly attenuated effect of the GRS on gout risk in the obese BMI group compared to the overweight BMI group, but no difference in the effect of the GRS between the low/normal BMI and overweight BMI groups, nor between the low/normal BMI and obese BMI groups. Conclusion: The association of a urate GRS with gout is mildly attenuated in obese individuals compared to overweight individuals. However, genetic variants have a strong effect on gout risk in those with overweight and obese BMIs, with an effect similar to that observed in low/normal BMI.