临床肝胆病杂志2024，Vol.40Issue(10)：1992-1999,8.DOI:10.12449/JCH241011
基于双向孟德尔随机化的不同BMI分型非酒精性脂肪性肝病与2型糖尿病的遗传关联分析
The genetic association between nonalcoholic fatty liver disease and type 2 diabetes mellitus in different body mass index categories:A bidirectional Mendelian randomization study
摘要
Abstract
Objective To investigate the genetic association between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)using bidirectional two-sample Mendelian randomization(MR),as well as the causal relationship between NAFLD and T2DM across different body mass index(BMI)categories.Methods The data were derived from genome-wide association studies conducted in European populations,with a sample size of 32 941 cases for NAFLD,312 646 cases for T2DM,and 681 275 cases for BMI.The univariate and multivariate MR methods were used to assess the bidirectional causal relationship between NAFLD and T2DM in the general population and across different BMI subtypes.The methods of inverse-variance weighting,MR-Egger regression,constrained maximum likelihood and model averaging,and weighted median were used to conduct the MR analysis,and MR-Pleiotropy Residual Sum and Outlier,radial MR,the MR-Egger intercept method,and the Cochrane Q test were used for sensitivity analysis.Results The univariate MR analysis revealed a bidirectional causal relationship between NAFLD and T2DM in the general population(forward analysis:odds ratio[OR]=9.75,95%confidence interval[CI]:2.57-37.00,P＜0.001;reverse analysis:OR=1.01,95%CI:1.00-1.01,P＜0.01).After adjustment for BMI,the multivariate MR analysis showed that the causal relationship between NAFLD and T2DM remained significant in the general population(OR=33.12,95%CI:7.57-144.95,P＜0.000 1).The subgroup analysis showed a causal relationship between NAFLD and T2DM across all BMI subtypes(lean subgroup:OR=12.19,95%CI:3.35-44.40,P＜0.001;overweight subgroup:OR=4.30,95%CI:1.69-10.92,P＜0.01;obese subgroup:OR=1.67,95%CI:1.14-2.44,P＜0.01).Conclusion This study reveals the causal relationship between NAFLD and T2DM in the general population of NAFLD and across different BMI subtypes from a genetic perspective.关键词
非酒精性脂肪性肝病/糖尿病,2型/身体质量指数/孟德尔随机化分析Key words
Non-alcoholic Fatty Liver Disease/Diabetes Mellitus,Type 2/Body Mass Index/Mendelian Randomization Analysis引用本文复制引用
段浩鑫,江宇泳,吴亭彧,熊飞翔,姜艳丹,张琴,赵赛赛,于浩..基于双向孟德尔随机化的不同BMI分型非酒精性脂肪性肝病与2型糖尿病的遗传关联分析[J].临床肝胆病杂志,2024,40(10):1992-1999,8.基金项目
北京市高层次公共卫生技术人才建设项目培养计划(学科带头人-03-04) （学科带头人-03-04）
首都卫生科研发展专项基金(首发2020-2-2172) Beijing Municipal High Rank Public Health Researcher Training Program(Discipline Leader-03-04) （首发2020-2-2172）
Capital Health Research and Development Project(2020-2-2172) （2020-2-2172）
