免疫细胞特征与骨质疏松症因果关系的双向孟德尔随机化研究  

The causal relationship between immune cell signatures and osteoporosis:a bidirectional mendelian randomization study

作　　者：王振宇 张洪美[1] 荆琳[1] 何名江[1] 闫奇[1] 唐海 李园源 刘思冶 陈彦百 王晓庆 WANG Zhenyu;ZHANG Hongmei;JING Lin;HE Mingjiang;YAN Qi;TANG Hai;LI Yuanyuan;LIU Siye;CHEN Yanbai;WANG Xiaoqing(Wangjing Hospital of CACMS,Beijing 100102,China)

机构地区：[1]中国中医科学院望京医院,北京100102

出　　处：《中医正骨》2024年第11期42-52,共11页The Journal of Traditional Chinese Orthopedics and Traumatology

摘　　要：目的:探讨免疫细胞特征与骨质疏松症(osteoporosis,OP)的因果关系。方法:分别从IEU OpenGWAS project数据库和FINNGEN数据库中筛选并获得731个免疫细胞特征的全基因组关联研究(genome-wide association study,GWAS)数据集和OP的GWAS数据集。基于工具变量筛选标准,筛选符合要求的免疫细胞特征的单核苷酸多态性(single nucleotide polymorphism,SNP)位点和OP的SNP位点。将筛选的免疫细胞特征的SNP位点作为工具变量,采用逆方差加权法(inverse variance weighted,IVW)、MR-Egger、加权中位数、简单模式和加权模式等进行正向孟德尔随机化(Mendelian randomization,MR)分析,评估免疫细胞特征与OP的因果关系。采用MR-presso检验进行水平多效性检验,采用Cochran’s Q检验评估IVW法和MR Egger法分析结果的异质性,采用留一法评估MR分析结果的稳定性。将筛选的OP的SNP位点作为工具变量,以正向MR分析获得的与OP具有可靠因果关系的免疫细胞特征为结局进行反向MR分析。结果:32个免疫细胞特征与OP存在可靠的因果关系,其中包含7个绝对细胞计数(absolute cell counts,AC)特征、13个中位荧光强度(median fluorescence intensity,MFI)特征、12个相对细胞计数(relative cell counts,RC)特征。在7个AC特征中,Sw mem AC、IgD^(-)CD38dim AC、HLA DR^(+)NK AC与OP呈负向因果关系,CD62L-myeloid DC AC、CD33br HLA DR+AC、DN(CD4^(-)CD8^(-))AC、CD25^(++)CD8br AC与OP呈正向因果关系;在13个MFI特征中,BAFF-R on IgD^(-)CD38br、CD3 on CD8br、CD3 on CD39^(+)CD4^(+)、CD16-CD56 on NK、CD28 on CD4 Treg、CD16 on CD14^(-)CD16^(+)monocyte、CD8 on TD CD8br与OP呈负向因果关系,CD19 on IgD-CD38br、CD86 on myeloid DC、HLA DR on CD14^(+)CD16^(-)monocyte、HLA DR on CD14^(+)monocyte、CD45 on CD33br HLA DR^(+)CD14^(-)、HLA DR on CD33br HLA DR^(+)CD14dim与OP呈正向因果关系;在12个RC特征中,IgD^(+)CD38dim%lymphocyte、CD11c^(+)CD62L^(-)monocyte%monocyte、TD CD8br%CD8br、CD39^(+)CD8br%T cell与Objective:To explore the causal relationship between immune cell signatures and osteoporosis(OP).Methods:The genome^(-)wide association study(GWAS)datasets about 731 immune cell signatures and OP were retrieved and extracted from the IEU OpenGWAS project database and FINNGEN database,respectively.According to the instrumental variable screening criteria,the eligible single nucleotide polymorphism(SNP)loci for immune cell signatures and OP were screened as the instrumental variables,and then a forward mendelian randomization(MR)analysis was conducted by using inverse variance weighted(IVW),MR-Egger regression,weighted median estimator,simple mode,and weighted mode to assess the causal relationship between immune cell signatures and OP.In addition,the horizontal pleiotropy was examined by MR-presso test,the heterogeneity of the results analyzed by IVW method and MR-egger regression was assessed by Cochran’s Q test,and the stability of the MR analysis results was evaluated by leave-one-out(LOO)test.Furthermore,a reverse MR analysis was conducted by taking the screened OP SNP loci as instrumental variable,and the immune cell signatures having a reliable causal relationship to OP obtained from the forward MR analysis as the outcome variable.Results:Seven absolute cell counts(AC)signatures,13 median fluorescence intensity(MFI)signatures and 12 relative cell counts(RC)signatures exhibited a reliable causal relationship with OP.Among the 7 AC signatures,the Sw mem AC,IgD^(-)CD38dim AC,and HLA DR^(+)NK AC showed a inverse causal relationship with OP,while the CD62L^(-)myeloid DC AC,CD33br HLA DR^(+)AC,DN(CD4^(-)CD8^(-))AC,and CD25^(++)CD8br AC presented a positive causal relationship with OP.Among the 13 MFI signatures,the BAFF^(-)R on IgD^(-)CD38br,CD3 on CD8br,CD3 on CD39^(+)CD4^(+),CD16^(-)CD56 on NK,CD28 on CD4 Treg,CD16 on CD14^(-)CD16^(+)monocyte,and CD8 on TD CD8br showed a inverse causal relationship with OP,while the CD19 on IgD^(-)CD38br,CD86 on myeloid DC,HLA DR on CD14^(+)CD16^(-)monocyte,HLA DR on CD14^(+)m

关 键 词：骨质疏松 免疫细胞特征 孟德尔随机化分析 全基因组关联研究 

分 类 号：R580[医药卫生—内分泌]