Genetic susceptibility, walking activity and the risk of incident gout

OBJECTIVES: Genetic predisposition increases the risk of gout, while walking activity may reduce it. We evaluated whether genetic predisposition modifies the association between walking activity and gout risk. METHODS: We included gout-free participants aged 40-70 years from the UK Biobank. Polygenic risk scores (PRS) were calculated using gout-associated single nucleotide polymorphisms, and participants were stratified into three strata according to PRS tertiles. Walking activity data were obtained from 7-day accelerometer recordings. Hazard ratios (HRs), risk differences (RDs) and 95% CIs for incident gout were estimated for moderate and high walking activity levels compared with the low activity within each PRS stratum. RESULTS: Among 86 930 participants (mean age: 61.9 years; 57.3% women), 672 developed gout over a 7-year follow-up. In the high PRS stratum, participants with moderate and high walking volumes had significantly lower rates of incident gout than those with low walking volumes, with HRs (95% CIs) of 0.68 (0.53, 0.87) and 0.55 (0.40, 0.75), respectively. The corresponding 7-year RDs (95% CIs) were -0.64% (-1.00%, -0.27%) and -0.81% (-1.18%, -0.45%). Similar inverse associations were observed in the moderate and low PRS strata. Additionally, higher walking intensity was associated with reduced gout risk across all PRS strata, with the protective effect being more pronounced in the high PRS stratum (P for additive interaction = 0.05). CONCLUSION: Higher walking activity was associated with a lower risk of gout across all levels of genetic predisposition, with the strongest effects observed in individuals with high genetic susceptibility.