免疫细胞与肥胖风险的因果关系:单变量双向及多变量孟德尔随机化研究  

Causal relationship between immune cells and obesity risk:Univariate bidirectional and multivariate Mendelian randomization study

作　　者：朱赟 林瑞芳 刘泳君 李雅[2] 郭志华 Zhu Yun;Lin Ruifang;Liu Yongjun;Li Ya;Guo Zhihua(School of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;Hunan Key Laboratory of Colleges and Universities of Intelligent Traditional Chinese Medicine Diagnosis and Preventive Treatment of Chronic Diseases,Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;Internet+TCM Diagnosis and Treatment of Chronic Diseases and Intelligent Application of Health Care Joint Postgraduate Training Base,Changsha 410208,Hunan,China)

机构地区：[1]湖南中医药大学中医学院,湖南长沙410208 [2]湖南中医药大学药学院,湖南长沙410208 [3]湖南中医药大学慢病中医智能诊断与治未病湖南省普通高等学校重点实验室,湖南长沙410208 [4]互联网+慢病中医诊治与养生智能化应用研究生联合培养基地,湖南长沙410208

出　　处：《生物医学转化》2024年第3期66-73,共8页Biomedical Transformation

基　　金：国家自然科学基金项目(82174343);湖南省重点研发计划项目(2022SK2012)。

摘　　要：目的利用孟德尔随机化方法,探讨免疫细胞与肥胖风险的因果关系。方法从GWAS catalog数据库获取731种免疫细胞与肥胖的数据集,采用逆方差加权法、加权中位数等方法探讨免疫细胞与肥胖的因果关系,并运用Cochran's Q检验、MR-Egger回归、Leave one out等方法,评价结果的稳定性。结果共发现32种免疫细胞与肥胖存在潜在因果关系(P<0.05),其中经典树突状细胞(cDC,CD80 on CD62L+myeloid DC,P<0.001)与肥胖因果关系最为稳定(P<0.001)。且与肥胖风险呈负向因果关系(OR=0.956,95%CI:0.931~0.982),同时反向孟德尔分析显示肥胖与TBNK细胞(CD45on lymphocyte,P=0.043,OR=1.372,95%CI:1.010~1.865)存在正向因果关系,即CD45 on lymphocyte与肥胖风险互为正向因果关系,经敏感性检验后,正反向结果均具有稳定性。多变量孟德尔分析显示,当32种免疫细胞性状同时激活时,仅TBNK细胞(CD16-CD56 on NK,P=0.016,OR=1.107,95%CI:1.019~1.203)与肥胖存在正向因果关系。结论本研究从遗传学的角度初步揭示免疫细胞与肥胖的因果关系,为未来的精准医学和个体化治疗提供重要的理论基础。Objective This study aims to explore the causal relationship between immune cells and obesity risk using the Mendelian randomization(MR)method.Methods Data sets for 731 types of immune cells and obesity were obtained from the Genome Wide Association Study(GWAS)catalog database.The inverse-variance weighted method,weighted median,and other methods were used to investigate the causal relationship between immune cells and obesity.The stability of the results was evaluated using Cochran's Q test,MR-Egger regression,and the leave-one-out method.Results A potential causal relationship(P<0.05)was identified between 32 types of immune cells and obesity.Among them,the causal relationship between classical dendritic cells(cDC,CD80 on CD62L+myeloid DC,P<0.001)and obesity was the most stable(P<0.001),showing a negative causal relationship with obesity risk(OR=0.956,95%CI:0.931-0.982).Additionally,reverse MR analysis revealed a positive causal relationship between obesity and TBNK cells(CD45 on lymphocytes,P=0.043,OR=1.372,95%CI:1.010-1.865),indicating a mutual positive causal relationship between CD45 on lymphocytes and obesity risk.Sensitivity analyses confirmed the stability of both forward and reverse results.Multivariate MR analysis showed that when all 32 immune cell traits were simultaneously activated,only TBNK cells(CD16-CD56 on NK cells,P=0.016,OR=1.107,95%CI:1.019-1.203)had a positive causal relationship with obesity.Conclusion This study preliminarily reveals the causal relationship between immune cells and obesity from a genetic perspective,providing an important theoretical basis for future precision medicine and individualized treatment.

关 键 词：免疫细胞 肥胖 孟德尔随机化 经典树突状细胞 TBNK细胞 

分 类 号：R723.14[医药卫生—儿科]