Healthy Lifestyle, Genetic Susceptibility and Risk of Kidney Stone Disease in the UK Biobank: A Prospective Cohort Study.

OBJECTIVE: To explore the association between modifiable lifestyle and kidney stone disease (KSD) risk, and to investigate whether genetic susceptibility modifies this association. PATIENTS AND METHODS: We included 300,875 participants without KSD from the UK Biobank cohort (recruited between March 13, 2006, and October 10, 2010) in this analysis. A healthy lifestyle score was constructed based on seven lifestyle items: regular physical activity, BMI < 25 kg/m2, lower sedentary time, adequate sleep duration, no smoking, adequate fluid intake, and a healthy diet. Based on this score, participants were classified into unfavorable, intermediate, and favorable lifestyle groups. Genetic susceptibility to KSD was assessed by a polygenic risk score. We employed Cox proportional hazards models to estimate HRs and 95% CIs for incident KSD. RESULTS: A total of 3,088 incident KSD cases were identified during a median follow-up of 12.3 years. Compared with the unfavorable lifestyle group, the multivariable-adjusted HR (95% CI) was 0.51 (0.44-0.59) for incident KSD in the favorable lifestyle group. No significant multiplicative interaction was observed (P for multiplicative interaction = .39), while a significant additive interaction was observed between an unfavorable lifestyle and high genetic susceptibility to KSD risk (relative excess risk due to interaction [RERI] = 1.14, 95% CI: 0.49-1.79). Compared with individuals with favorable lifestyle and low genetic susceptibility, the HR (95% CI) for those with unfavorable lifestyle and high genetic risk was 3.08 (2.49-3.80). CONCLUSIONS: Healthy lifestyle was inversely associated with KSD risk, and a significant additive interaction was observed between lifestyle and genetic susceptibility.