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

Xinyuan Ge; Xiao Wang; Yuqian Yan; Lu Zhang; Chengxiao Yu; Jing Lu; Xin Xu; Jiaxin Gao; Maojie Liu; Tao Jiang; Bibo Ke; Ci Song

doi:10.1111/liv.15588

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

Liver Int. 2023 Jun;43(6):1287-1297. doi: 10.1111/liv.15588. Epub 2023 Apr 23.

Authors

Xinyuan Ge¹, Xiao Wang^{1

2}, Yuqian Yan¹, Lu Zhang¹, Chengxiao Yu^{1

3}, Jing Lu^{1

4}, Xin Xu¹, Jiaxin Gao¹, Maojie Liu¹, Tao Jiang¹, Bibo Ke⁵, Ci Song^{1

6}

Affiliations

¹ Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
² Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
⁴ Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁶ Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, China.

PMID: 37088982
DOI: 10.1111/liv.15588

Abstract

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 (p_trend < .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.

Keywords: additive interaction; genetic susceptibility; nonalcoholic fatty liver disease; physical activity; sedentary behaviour.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Specimen Banks
Genetic Predisposition to Disease
Humans
Liver
Membrane Proteins / genetics
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / genetics
Polymorphism, Single Nucleotide
Prospective Studies
Risk Factors
United Kingdom / epidemiology

Substances

Membrane Proteins