Circadian syndrome and its components in relation to incident gastroesophageal reflux disease: a prospective cohort study from the UK Biobank

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Abstract
Circadian Syndrome (CircS), a cluster encompassing metabolic dysregulation, short sleep duration, and depression, has been implicated in various chronic diseases. Gastroesophageal reflux disease (GERD) is a highly prevalent digestive disorder; however, its prospective association with CircS remains unclear. This prospective cohort study utilized data from the UK Biobank, including 330,925 participants free of GERD at baseline. CircS was defined as meeting at least four of seven components. The primary outcome was incident GERD, identified through the first recorded diagnosis code from linked hospital, primary care, death registry, and self-report data. Cox proportional hazards models were used to estimate hazard ratios with sequential adjustments for demographics, socioeconomic status, lifestyle factors, and medication use. Over a median follow-up of 13.05 years, 28,554 incident GERD cases were documented. In the fully adjusted model, CircS was associated with a significantly increased risk of GERD (HR = 1.20; 95% CI: 1.16-1.23). All seven individual components were each associated with GERD risk in separate fully adjusted models, with the strongest associations observed for depression (HR = 1.38) and short sleep (HR = 1.29). A significant dose-response relationship was evident as the number of components increased. Subgroup analyses revealed stronger associations among individuals aged under 65 years, women, non-White participants, and those not using proton pump inhibitors. Circadian Syndrome is independently associated with incident GERD, with depression and short sleep as core driving components. These findings support the integration of circadian, metabolic, and psychological health assessments into GERD risk stratification.
Funding Information
  • Central Incentive Fund for Regional S&T Development (25ZYJA024)
  • Gansu Provincial Major Scientific Research Project on Health Industry Innovation (GSWSZD2025-04)

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