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

Abstract

To explore the association between modifiable lifestyle and kidney stone disease (KSD) risk, and to investigate whether genetic susceptibility modifies this association. 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. 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). Healthy lifestyle was inversely associated with KSD risk, and a significant additive interaction was observed between lifestyle and genetic susceptibility.