Sleep patterns, genetic susceptibility, and digestive diseases: a large-scale longitudinal cohort study

Abstract

Background: Sleep problems are prevalent. However, the impact of sleep patterns on digestive diseases remains uncertain. Moreover, the interaction between sleep patterns and genetic predisposition with digestive diseases has not been comprehensively explored.

Methods: Four hundred ten thousand five hundred eighty-six participants from UK Biobank with complete sleep information were included in the analysis. Sleep patterns were measured by sleep scores as the primary exposure, based on five healthy sleep behaviors. Individual sleep behaviors were secondary exposures. Genetic risk of the digestive diseases was characterized by polygenic risk score. Primary outcome was incidence of 16 digestive diseases.

Results: Healthy sleep scores showed dose-response associations with reduced risks of digestive diseases. Compared to participants scoring 0-1, those scoring 5 showed a 28% reduced risk of any digestive disease, including a 50% decrease in irritable bowel syndrome, 37% in non-alcoholic fatty liver disease, 35% in peptic ulcer, 34% in dyspepsia, 32% in gastroesophageal reflux disease, 28% in constipation, 25% in diverticulosis, 24% in severe liver disease, and 18% in gallbladder disease, whereas no correlation was observed with inflammatory bowel disease and pancreatic disease. Participants with poor sleep and high genetic risk exhibited approximately a 60% increase in the risk of digestive diseases. A healthy sleep pattern is linked to lower digestive disease risk in participants of all genetic risk levels.

Conclusions: In this large population-based cohort, a healthy sleep pattern was associated with a reduced risk of digestive diseases, regardless of genetic susceptibility. The authors' findings underscore the potential impact of healthy sleep traits in mitigating the risk of digestive diseases.

Figure 1

Overview of study design. (A) The main digestive system organs that suffer from digestive system diseases. Secondary outcomes are listed below each organ. (B) A healthy sleep score was constructed according to five sleep traits and defined the low-risk groups as follows: early chronotype, sleep 7–8 h per day, never/rarely insomnia, no snoring, and no frequent excessive daytime sleepiness. Digestive diseases were defined based on ICD-10. Cox proportional hazards models were used to investigate the association between sleep patterns and the risk of digestive diseases. Genetic risk was characterized by polygenic risk score. UKB, UK Biobank. ICD-10, the 10th revision of the International Classification of Diseases. Image was cited from smart.servier.com. GERD: gastroesophageal reflux disease; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; KM, Kaplan–Meier; NAFLD, non-alcohol fatty liver disease.

Figure 2

Flow chart of eligible participants’ selection. IPTW, inverse probability of treatment weighting; PRS, ploygenic risk score.

Figure 3

Association of healthy sleep score with digestive disease. Incident risk of digestive diseases according to healthy sleep score. Incident risk of digestive diseases according to healthy sleep score in model adjusted for age, sex, ethnicity, BMI, Townsend Deprivation Index, household income, education, acid inhibitor use, recent hospital admissions, smoking status, alcohol consumption and physical activity and comorbidities, including hypertension, heart failure, myocardial infarction, stroke, asthma, renal failure, chronic obstructive pulmonary disease, thyroid disease, anxiety, depression, dementia, and diabetes. GERD, gastroesophageal reflux disease; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; NAFLD, non-alcoholic fatty liver disease.

Figure 4

The interaction of genetic risk and sleep pattern with digestive diseases. (A) Dyspepsia; (B) IBS; (C) Constipation; (D) Gastric ulcer; (E) GERD; (F) Cholelithiasis; (G) NAFLD; (H) Diverticulosis. Multivariable model was adjusted for age, sex, ethnicity, BMI, the Townsend Deprivation Index, physical activity, household income, smoking status, alcohol consumption, acid inhibitor use, recent hospital admissions, education, and comorbidities. The vertical line indicates the reference value of 1. GERD, gastroesophageal reflux disease; HR, hazard ratio; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; NAFLD, non-alcoholic fatty liver disease.