Birthweight, Childhood Obesity, Adulthood Obesity and Body Compositions, and Gastrointestinal Diseases: A Mendelian Randomization Study

Abstract

Background: Obesity has been established as a risk factor for several gastrointestinal diseases, whether the associations are causal is uncertain. In addition, the associations of obesity-related factors with gastrointestinal diseases have been scarcely explored. This Mendelian randomization aimed to investigate the associations of birth weight, childhood body mass index (BMI), adulthood BMI and waist-hip ratio, and body composition with the risk of 24 gastrointestinal diseases. Methods: Independent genetic instruments associated with the exposures at the genome-wide significance level were selected from corresponding large-scale genome-wide association studies. Summary-level data for gastrointestinal diseases were obtained from the UK Biobank and large consortia. Results: Genetically predicted higher levels of birth weight was associated with a lower risk of gastroesophageal reflux. Genetically predicted higher childhood BMI was associated with an increased risk of duodenal ulcer, non-alcoholic fatty liver disease, and cholelithiasis. However, the associations did not persist after adjusting for genetically predicted adulthood BMI. Genetically predicted higher adulthood BMI and waist-hip ratio were associated with 19 and 17 gastrointestinal diseases, respectively. Genetically predicted greater visceral adiposity was associated with an increased risk of 18 gastrointestinal diseases. There were no strong associations between genetically predicted whole body fat and fat-free mass indices with gastrointestinal diseases. Conclusion: This study suggests that greater adulthood adiposity, measured as either BMI, waist-hip ratio, or visceral adipose tissue, is causally associated with an increased risk of a broad range of gastrointestinal diseases.

Functional investigation and two-sample Mendelian randomization study of non-alcoholic fatty liver disease hub genes obtained by WGCNA

“…Mendelian randomization (MR) has gained prominence in recent years as a robust method for inferring potential causal relationships by utilizing single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to assess the causal relationship between exposure factors and outcomes. The advantages of MR include its ability to provide causal inference, overcome confounding factors, and avoid reverse causality bias by utilizing genetic variants assigned at random [8,9].…”