Journal of affective disordersJan 10, 2024

Sleep patterns, genetic risk, and chances of chronic liver disease in 408,560 UK adults

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

During a median 12.5 years of follow-up, 10,915 incident cases of chronic liver disease (CLD) were documented among 408,560 participants initially free of the disease.

A healthy sleep pattern, defined by factors such as sleep duration of 7-8 hours and no insomnia, is associated with a reduced risk of developing CLD.
Participants with a sleep score of 5 had a hazard ratio of 0.54 for CLD compared to those with a score of 0-1.
The hazard ratios for specific CLD types indicated significant reductions: 0.52 for viral hepatitis, 0.47 for non-alcoholic fatty liver disease (NAFLD), 0.57 for cirrhosis, 0.32 for alcoholic liver disease, and 0.53 for liver cancer.
Higher genetic risk related to the PNPLA3 gene may increase the likelihood of developing CLD in individuals with unhealthy sleep patterns.
The interaction between healthy sleep patterns and PNPLA3 genetic risk accounted for a relative excess risk of 0.05 and an attributable proportion of 13% for CLD.

Simplified

BACKGROUND: Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk.

METHODS: We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7-8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk.

RESULTS: During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0-1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %).

LIMITATIONS: Measurement error was unavoidable for self-reported data on sleep behaviors.

CONCLUSIONS: Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

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Declaration of competing interest All authors declare no support from companies for the submitted work; no relationships with companies that might have an interest in the submitted work in the previous three years; no spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and no nonfinancial interests that may be relevant to the submitted work.

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Sleep patterns, genetic risk, and chances of chronic liver disease in 408,560 UK adults

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