Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis

Jie Chen; Xixian Ruan; Tian Fu; Shiyuan Lu; Dipender Gill; Zixuan He; Stephen Burgess; Edward L Giovannucci; Susanna C Larsson; Minzi Deng; Shuai Yuan; Xue Li

doi:10.1016/j.ebiom.2024.105110

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysis

EBioMedicine. 2024 Apr 6:103:105110. doi: 10.1016/j.ebiom.2024.105110. Online ahead of print.

Authors

Jie Chen¹, Xixian Ruan², Tian Fu², Shiyuan Lu³, Dipender Gill⁴, Zixuan He⁵, Stephen Burgess⁶, Edward L Giovannucci⁷, Susanna C Larsson⁸, Minzi Deng⁹, Shuai Yuan¹⁰, Xue Li¹¹

Affiliations

¹ School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.
² Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.
³ Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁵ Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China.
⁶ MRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁷ Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA.
⁸ Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
⁹ Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: dengmz@csu.edu.cn.
¹⁰ Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: shuai.yuan@ki.se.
¹¹ School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK. Electronic address: xue.li@ed.ac.uk.

Abstract

Background: The causal associations of physical activity and sedentary behavior with the risk of gastrointestinal disease are unclear. We performed a Mendelian randomization analysis to examine these associations.

Methods: Genetic instruments associated with leisure screen time (LST, an indicator of a sedentary lifestyle) and moderate-to-vigorous intensity physical activity (MVPA) at the genome-wide significance (P < 5 × 10^-8) level were selected from a genome-wide association study. Summary statistics for gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analyses were conducted for genetically determined LST with adjustment for MVPA and vice versa. We also performed multivariable MR with adjustment for genetically proxied smoking, body mass index (BMI), waist-to-hip ratio, type 2 diabetes, and fasting insulin for both exposures.

Findings: Genetically proxied longer LST was associated with an increased risk of gastrointestinal reflux, gastric ulcer, duodenal ulcer, chronic gastritis, irritable bowel syndrome, diverticular disease, Crohn's disease, ulcerative colitis, non-alcoholic fatty liver disease, alcoholic liver disease, cholangitis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and acute appendicitis. Most associations remained after adjustment for genetic liability to MVPA. Genetic liability to MVPA was associated with decreased risk of gastroesophageal reflux, gastric ulcer, chronic gastritis, irritable bowel syndrome, cholecystitis, cholelithiasis, acute and chronic pancreatitis. The associations attenuated albeit directionally remained after adjusting for genetically predicted LST. Multivariable MR analysis found that BMI and type 2 diabetes mediated the associations of LST and MVPA with several gastrointestinal diseases.

Interpretation: The study suggests that a sedentary lifestyle may play a causal role in the development of many gastrointestinal diseases.

Funding: Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), Natural Science Foundation of Hunan Province (2021JJ30999), Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), Swedish Research Council (Vetenskapsrådet, 2019-00977), Swedish Cancer Society (Cancerfonden), the Wellcome Trust (225790/7/22/Z), United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and National Institute for Health Research Cambridge Biomedical Research Centre (NHIR203312).

Keywords: Gastrointestinal diseases; Leisure screen time; Mendelian randomization; Physical activity; Sedentary lifestyle.