Pear-shaped body types linked to lower risk of gout: genetic evidence from Mendelian randomization.

Background: Growing evidence has indicated an association between obesity, measured by body mass index (BMI), and urate levels, as well as the risk of gout. However, BMI inadequately reflects the body's fat distribution, including variations in gluteofemoral, abdominal subcutaneous, and visceral adipose tissue (GFAT, ASAT, and VAT). This study aimed to utilize Mendelian randomization (MR) to investigate the causal associations between genetically predicted fat distribution, urate levels, and the risk of gout.

Methods: We performed a comprehensive investigation of nine fat distribution traits, including raw and adjusted measures of GFAT, ASAT, VAT, and their corresponding ratios, as potential exposures. Using two-sample MR analysis, we investigated the causal associations between these fat distribution traits, urate levels, and gout risk. Additionally, we conducted multivariate MR analysis to assess whether the interaction between different fat depots influenced causal effects. Furthermore, we applied a two-step MR analysis to assess their mediating effects on gout risk through urate levels. We also conducted multiple sensitivity analyses to confirm the robustness and validity of our results.

Results: The MR analysis revealed a significant negative causal association between GFAT (both raw and adjusted) and urate levels as well as gout risk. Conversely, a significant positive causal association was observed between ASAT and urate levels. The mediation analysis revealed that 36% and 40% of the protective effect of raw and adjusted GFAT on the risk of gout was mediated by urate level, respectively. These findings remained consistent across multivariable analyses.

Conclusions: This study provides preliminary evidence supporting the association between fat distribution, urate levels, and gout risk, suggesting a potential lower risk of gout in individuals with a pear-shaped body.