免疫细胞在骨质疏松症中的作用:一项孟德尔随机化研究

Role of Immune Cells in Osteoporosis: A Mendelian Randomization Study

目的:采用双向孟德尔随机化(Mendelian Randomization, MR)分析探讨免疫细胞与骨质疏松(Osteoporosis, OP)的因果关系,为进一步阐明OP的发生发展提供方向,并指导临床治疗。方法:使用全基因组关联分析(GWAS)数据库的公开数据,运用逆方差加权法(IVW),MR-Egger,加权中位数法,简单模式法(Simple mode),加权模式法(Weighted mode)进行MR分析,评估免疫细胞与骨质疏松的因果关系。结果:MR分析表明有11种免疫细胞表型在IVW和WM两种MR方法均有显著因果影响,其中(CD25 on CD45RA + CD4 not Treg、CD86 on myeloid DC、EM CD4 + AC、IgD on unsw mem) 4个免疫细胞表型对OP的发生成正相关,(CD16 +% monocyte, CD25 on CD4 +、HLA DR + NK% CD3 – lymphocyte, HLA DR + NK% NK、IgD + CD24 +% B cell, Memory B cell% B cell, SSC − A on monocyte) 7个免疫细胞表型对OP的发生成负相关。反向MR分析表明,OP可使(HLA DR + + monocyte% monocyte, HLA DR + + monocyte% leukocyte, HLA DR + + monocyte Absolute Count)三种免疫细胞下降。结论:MR分析结果显示有11种免疫细胞表型对OP均有显著因果影响,反向MR研究显示OP对3种免疫细胞表型有因果影响。Objective: To investigate the causal relationship between immune cells and osteoporosis (OP) by Mendelian Randomization (MR) analysis, and to provide direction for further elucidating the occurrence and development of OP and guiding clinical treatment. Methods: MR analysis was performed using public data from the genome-wide association analysis (GWAS) database using inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode to assess the causal relationship between immune cells and osteoporosis. Results: MR analysis showed that 11 immune cell phenotypes had significant causal effects in IVW and WM MR methods, of which 4 immune cell phenotypes (CD25 on CD45RA + CD4 not Treg, CD86 on myeloid DC, EM CD4 + AC, IgD on unsw mem) were positively correlated with the occurrence of OP, and 7 immune cell phenotypes (CD16 +% monocyte, CD25 on CD4 +, HLA DR + NK% CD3 − lymphocyte, HLA DR + NK% NK, IgD + CD24 +% B cell, Memory B cell% B cell, SSC − A on monocyte) were negatively correlated with the occurrence of OP. Reverse MR analysis showed that OP decreased three immune cells (HLA DR + + monocyte% monocyte, HLA DR + + monocyte% leukocyte, HLA DR + + monocyte Absolute Count). Conclusion: MR analysis showed that 11 immune cell phenotypes had a significant causal effect on OP, and reverse MR study showed that OP had a causal effect on 3 immune cell phenotypes.