Behavioural activity pattern, genetic factors, and the risk of nonalcoholic fatty liver disease: A prospective study in the UK Biobank

• Published in: Liver international Vol. 43; no. 6; pp. 1287 - 1297
• Main Authors: Ge, Xinyuan, Wang, Xiao, Yan, Yuqian, Zhang, Lu, Yu, Chengxiao, Lu, Jing, Xu, Xin, Gao, Jiaxin, Liu, Maojie, Jiang, Tao, Ke, Bibo, Song, Ci
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2023
• Subjects: Activity patterns; additive interaction; Biobanks; Biological Specimen Banks; Fatty liver; Genetic analysis; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; genetic susceptibility; Genetic variance; Health risk assessment; Humans; Liver; Liver diseases; Membrane Proteins - genetics; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - genetics; nonalcoholic fatty liver disease; Physical activity; Polymorphism, Single Nucleotide; Prospective Studies; Risk; Risk Factors; sedentary behaviour; United Kingdom - epidemiology; United Kingdom; United Kingdom > UK; sedentary behaviour; nonalcoholic fatty liver disease; genetic susceptibility; additive interaction; physical activity
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/liv.15588

Background & Aims Physical activity, sedentary behaviour, and genetic variants have been associated with the nonalcoholic fatty liver disease (NAFLD). However, whether and how the degree of healthy activity patterns may modify the impact of genetic susceptibility on NAFLD remains unknown. Methods Behaviour activity factors were determined according to total physical activity (TPA) and sedentary time. The polygenic risk score (PRS) was calculated by variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Cox regression was used to analyse the associations of genetic and behaviour activity factors with incident NAFLD in the UK Biobank (N = 338 087). Results During a median follow‐up of 12.4 years, 3201 incident NAFLD cases were ascertained. Analyses of TPA and sedentary time simultaneously showed a dose–response association with the risk of NAFLD (ptrend < .001). The association of behaviour activity patterns with NAFLD varied by genetic variants. Of the subjects with high genetic risk, we observed a null protective effect of moderate or high TPA on NAFLD risk, while sitting less than three hours a day significantly decreased the risk of NAFLD (p = 3.50 × 10−4). The high genetic risk of NAFLD can also be offset by the combination of moderate physical activity and shorter sedentary time. Moreover, the high genetic risk group has the greatest reduction of 10‐year absolute risk (6.95 per 1000 person‐years) if reaching both healthy activities. Conclusions Moderate‐to‐high physical activity and favourable sedentary behaviour may be lifestyle modifications in preventing NAFLD, which could offset the harmful effect of predisposing genetic factors.