Causal Association Of Imaging-measured Abdominal Subcutaneous Adipose Tissue With Gastrointestinal Disease

Objective: Epidemiological studies have shown that abdominal obesity is positively correlated with gastrointestinal related diseases such as gastric ulcer,inflammatory bowel disease,gastric cancer and colorectal cancer.However,the causal relationship between abdominal subcutaneous adipose tissue and risk of gastrointestinal-related diseases remains unclear.Two-sample Mendelian randomization(2SMR)may better use genetic variants identified in genome-wide association studies(GWAS)based on radiographically measured abdominal adipose tissue(ASAT)as instrumental variables(IVs)to infer the causal relationship between outcomes and exposure.The aim of this study was to implement a two-sample MR study design using the latest and most comprehensive ASAT-related GWAS data to investigate whether there is a causal relationship between genetically predicted ASAT and gastrointestinal-related disorders.Methods: We used a 2SMR study to examine the potential causal association and the magnitude of the association between ASAT and gastrointestinal-related disease risk.In this study,single nucleotide polymorphisms(SNPs)associated with ASAT were selected as instrumental variables and summary-level GWAS data for gastric ulcer,IBD,gastric cancer,and colorectal cancer were obtained,respectively.All statistical analyzes were performed using R software,all of which were two-sided tests,with P<0.05 as the test standard.The IVW model was the main method used in this 2SMR analysis,and MREgger,weighted model,simple model,and weighted median were used for quality control.Sensitivity analysis was performed using the leave-one-out method.The MR-Egger model uses the Q test to verify the heterogeneity of IVs,and the MR-Egger regression method performs hypothesis testing on the pleiotropic effect of IVs.Results: 62 SNPs were screened out as IVs associated with ASAT.IVW analysis showed that genetically determined ASAT was significantly and positively associated with increased risk of IBD(OR=1.18;95%CI=1.03-1.35;P=0.02).However,there was no significant causal relationship between ASAT and the other three gastrointestinal related diseases,such as gastric ulcer(OR=1.00;95%CI=0.99-1.01;P=0.69),gastric cancer(OR=0.87;95%CI=0.57-1.33;P=0.51)and colorectal cancer(OR=1.12;95 %CI=0.91-1.37;P=0.29).The heterogeneity estimated by MR-Egger model(inflammatory bowel disease Q=58.03;P=0.32),(colorectal cancer Q=39.29;P=0.86),(gastric ulcer Q=55.88;P=0.51)and(gastric cancer Q=34.69;P=0.95)All P values were much greater than 0.05,indicating that there was no heterogeneity among IVs.The leave-one-out method did not observe significant association changes after removing any IVs,which would not have a fundamental impact on the results,suggesting that the results of this study are relatively robust.Conclusion: Abdominal subcutaneous adipose tissue is associated with increased risk of IBD.This study provides evidence for a causal association between ASAT and IBD risk.However,the conclusion still needs to be verified by future large-scale intervention experiments.