Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysisResearch in context

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

EBioMedicine (May 2024)

Sedentary lifestyle, physical activity, and gastrointestinal diseases: evidence from mendelian randomization analysisResearch in context

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

Affiliations

Jie Chen: 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
Xixian Ruan: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
Tian Fu: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
Shiyuan Lu: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
Dipender Gill: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
Zixuan He: Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China
Stephen Burgess: MRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Edward L. Giovannucci: 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
Susanna C. Larsson: 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
Minzi Deng: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China; Corresponding author. Department of Gastroenterology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, China.
Shuai Yuan: Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Corresponding author.
Xue Li: 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; Corresponding author. Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Journal volume & issue: Vol. 103
p. 105110

Abstract

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Summary: 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).

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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