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

作　　者：段浩鑫 江宇泳[2] 吴亭彧 熊飞翔 姜艳丹 张琴[1] 赵赛赛 于浩[2] DUAN Haoxin;JIANG Yuyong;WU Tingyu;XIONG Feixiang;JIANG Yandan;ZHANG Qin;ZHAO Saisai;YU Hao(Graduate School,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Department of Integrative Medicine,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China)

机构地区：[1]北京中医药大学东直门医院研究生院,北京100700 [2]首都医科大学附属北京地坛医院中西医结合中心,北京100015

出　　处：《临床肝胆病杂志》2024年第10期1992-1999,共8页Journal of Clinical Hepatology

基　　金：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);首都卫生科研发展专项基金(首发2020-2-2172)。

摘　　要：目的运用双向双样本孟德尔随机化(MR)评估非酒精性脂肪性肝病(NAFLD)与2型糖尿病(T2DM)的遗传关联,并进一步探讨不同BMI的NAFLD人群与T2DM的因果关系。方法数据来源于以欧洲人群为研究对象的全基因组关联研究,其中NAFLD的样本量为32941例,T2DM为312646例,BMI为681275例。运用单变量、多变量MR方法评估NAFLD总人群及各BMI亚型与T2DM之间的双向因果关系。采用逆方差加权法、MR-Egger回归、约束最大似然与模型平均法、加权中位数法进行MR分析,采用MR多效性残差和与离群值、径向MR、MR-Egger截距法、Cochran Q检验进行敏感性分析。结果单变量MR分析显示NAFLD总人群与T2DM之间存在双向因果关系(正向OR=9.75,95%CI:2.57~37.00,P<0.001;反向OR=1.01,95%CI:1.00~1.01,P<0.01)。多变量MR分析显示经BMI校正后,NAFLD总人群与T2DM的因果关系仍然保持显著(OR=33.12,95%CI:7.57~144.95,P<0.0001)。亚组分析显示,NAFLD各亚组均与T2DM存在因果关系(瘦型OR=12.19,95%CI:3.35~44.40,P<0.001;超重型OR=4.30,95%CI:1.69~10.92,P<0.01;肥胖型OR=1.67,95%CI:1.14~2.44,P<0.01)。结论本研究从遗传学层面揭示了NAFLD总人群及各BMI亚型与T2DM之间的因果关系。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 genomewide association studies conducted in European populations,with a sample size of 32941 cases for NAFLD,312646 cases for T2DM,and 681275 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 inversevariance 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<0.0001).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 

分 类 号：R575.5[医药卫生—消化系统] R587.1[医药卫生—内科学]