The roles of lifestyle factors and genetic risk in the association between night shift work and cholelithiasis: a prospective cohort study

Abstract

AbstractBackgroundNight shift work has been linked to various adverse health outcomes, but its relationship with incident cholelithiasis remains unclear. This study aims to investigate the association between night shift work and the risk of cholelithiasis, assess the potential modifying effects of genetic susceptibility, and explore the mediating roles of lifestyle factors.MethodsA total of 219,810 subjects who were either in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment were collected. Genetic risk was quantified and stratified by a polygenic risk score (PRS) incorporating 13 known cholelithiasis-associated loci. We used Cox proportional hazard models to investigate associations between night shift work and risk of cholelithiasis. Lifestyle factors measured at baseline were explored as potential mediators.ResultsDuring a median follow-up of 13.76 years, 6450 incidents of cholelithiasis were documented. Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of cholelithiasis was 1.09 (1.01, 1.17) for individuals with rarely/some night shifts and 1.18 (1.04, 1.35) for those with usual/permanent night shifts. Among the 62,558 participants who had reports on lifetime experience of night shift work, those with a higher frequency of night shifts and a longer length of each night shift were associated with an increased risk of cholelithiasis. Notably, individuals with usual/permanent night shifts and high genetic risk exhibited the highest risk of cholelithiasis (HR: 1.48, 95% CI: 1.21, 1.81), with day workers at low genetic risk serving as the reference. Mediation analysis indicated that a substantial portion (24.6%) of the association was mediated by BMI, followed by unhealthy alcohol intake (4.5%) and sedentary time (1.8%).ConclusionsNight shift work is associated with an increased risk of cholelithiasis, with this relationship being largely mediated by lifestyle factors. These findings suggest that reducing the frequency and duration of night shifts may help mitigate the incidence of cholelithiasis among night shift workers, particularly for those with heightened genetic susceptibility.