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[1]王振宇,張洪美,荊琳,等.免疫細(xì)胞特征與骨質(zhì)疏松癥因果關(guān)系的雙向孟德?tīng)栯S機(jī)化研究[J].中醫(yī)正骨,2024,36(11):42-52.
　WANG Zhenyu,ZHANG Hongmei,JING Lin,et al.The causal relationship between immune cell signatures and osteoporosis:a bidirectional mendelian randomization study[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(11):42-52.
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免疫細(xì)胞特征與骨質(zhì)疏松癥因果關(guān)系的雙向孟德?tīng)栯S機(jī)化研究()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期數(shù):
2024年11期
頁(yè)碼:
42-52
欄目:
數(shù)據(jù)庫(kù)研究
出版日期:
2024-11-20

文章信息/Info

Title:
The causal relationship between immune cell signatures and osteoporosis:a bidirectional mendelian randomization study
作者:
王振宇; 張洪美; 荊琳; 何名江; 閆奇; 唐海; 李園源; 劉思冶; 陳彥百; 王曉慶
中國(guó)中醫(yī)科學(xué)院望京醫(yī)院,北京 100102
Author(s):
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
關(guān)鍵詞:
骨質(zhì)疏松;  免疫細(xì)胞特征;  孟德?tīng)栯S機(jī)化分析;  全基因組關(guān)聯(lián)研究
Keywords:
osteoporosis;  immune cell characteristics;  Mendelian randomization analysis;  genome-wide association study
摘要:
目的:探討免疫細(xì)胞特征與骨質(zhì)疏松癥(osteoporosis,OP)的因果關(guān)系。方法:分別從IEU OpenGWAS project數(shù)據(jù)庫(kù)和FINNGEN數(shù)據(jù)庫(kù)中篩選并獲得731個(gè)免疫細(xì)胞特征的全基因組關(guān)聯(lián)研究(genome-wide association study,GWAS)數(shù)據(jù)集和OP的GWAS數(shù)據(jù)集。基于工具變量篩選標(biāo)準(zhǔn),篩選符合要求的免疫細(xì)胞特征的單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)位點(diǎn)和OP的SNP位點(diǎn)。將篩選的免疫細(xì)胞特征的SNP位點(diǎn)作為工具變量,采用逆方差加權(quán)法(inverse variance weighted,IVW)、MR-Egger、加權(quán)中位數(shù)、簡(jiǎn)單模式和加權(quán)模式等進(jìn)行正向孟德?tīng)栯S機(jī)化(Mendelian randomization,MR)分析,評(píng)估免疫細(xì)胞特征與OP的因果關(guān)系。采用MR-presso檢驗(yàn)進(jìn)行水平多效性檢驗(yàn),采用Cochran's Q檢驗(yàn)評(píng)估IVW法和MR Egger法分析結(jié)果的異質(zhì)性,采用留一法評(píng)估MR分析結(jié)果的穩(wěn)定性。將篩選的OP的SNP位點(diǎn)作為工具變量,以正向MR分析獲得的與OP具有可靠因果關(guān)系的免疫細(xì)胞特征為結(jié)局進(jìn)行反向MR分析。結(jié)果:32個(gè)免疫細(xì)胞特征與OP存在可靠的因果關(guān)系,其中包含7個(gè)絕對(duì)細(xì)胞計(jì)數(shù)(absolute cell counts,AC)特征、13個(gè)中位熒光強(qiáng)度(median fluorescence intensity,MFI)特征、12個(gè)相對(duì)細(xì)胞計(jì)數(shù)(relative cell counts,RC)特征。在7個(gè)AC特征中,Sw mem AC、IgD-CD38dim AC、HLA DR+NK AC與OP呈負(fù)向因果關(guān)系,CD62L-myeloid DC AC、CD33br HLA DR+AC、DN(CD4-CD8-)AC、CD25++ CD8br AC與OP呈正向因果關(guān)系; 在13個(gè)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與OP呈負(fù)向因果關(guān)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與OP呈正向因果關(guān)系; 在12個(gè)RC特征中,IgD+CD38dim%lymphocyte、CD11c+CD62L-monocyte%monocyte、TD CD8br%CD8br、CD39+CD8br%T cell與OP呈負(fù)向因果關(guān)系,IgD-CD38dim%B cell、CD62L-DC%DC、CD8br%leukocyte、CD8br and CD8dim%leukocyte、NKT%T cell、NKT%lymphocyte、HLA DR+CD8br%lymphocyte、CD3-lymphocyte%leukocyte與OP呈正向因果關(guān)系。結(jié)論:部分免疫細(xì)胞特征與OP之間存在因果關(guān)系,這為探究免疫系統(tǒng)與OP間的作用機(jī)制提供了線(xiàn)索和方向。
Abstract:
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+monocyte,CD45 on CD33br HLA DR+CD14-,HLA DR on CD33br HLA DR+CD14dim presented a positive causal relationship with OP.Among the 12 RC signatures,the IgD+CD38dim%lymphocyte,CD11c+CD62L-monocyte%monocyte,TD CD8br%CD8br,and CD39+CD8br%T cell showed a inverse causal relationship with OP,while the IgD-CD38dim%B cell,CD62L-DC%DC,CD8br%leukocyte,CD8br and CD8dim%leukocyte,NKT%T cell,NKT%lymphocyte,HLA DR+CD8br%lymphocyte,and CD3-lymphocyte%leukocyte presented a positive causal relationship with OP.Conclusion:A causality exists between partial immune cell signatures and OP,which provides the clues and directions for exploring the mechanism of action between the immune system and OP.

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