免疫细胞与炎性关节病风险的因果关系:一项孟德尔随机化研究

Causal Relationship Between Immune Cells and Risk of Inflammatory Joint Diseases:A Mendelian Randomization Study

目的运用两样本孟德尔随机化的方法,探讨免疫细胞与炎性关节病风险的因果关系。方法从Finngen数据库、GWAS catalog数据库获取731种免疫细胞与骨关节炎、强直性脊柱炎、痛风、银屑病关节炎的数据集。运用逆方差加权法、加权中位数法和MR-Egger法探讨免疫细胞与骨关节疾病的因果关系,并运用Cochran′s Q检验、MR-Egger回归、MR-PRESSO、Leave one out法和Meta分析,评价研究结果的稳定性和可靠性。结果共得到45个免疫细胞与骨关节炎、35个免疫细胞与强直性脊柱炎、29个免疫细胞与痛风、36个免疫细胞与银屑病关节炎存在潜在因果关系(P<0.05),其中HLA DR on CD14-CD16+monocyte与强直性脊柱炎存在显著因果关系(P<6.8×10^(-5)),结果具有稳定性,但Meta分析显示因果关系不显著(OR=1.00,95%CI:1.00~1.00)。结论本研究从遗传学的角度,初步揭示免疫细胞与强直性脊柱炎为代表的炎性关节病的因果关系,为未来的精准医学和个体化治疗提供重要的理论基础。

Objective A two-sample Mendelian randomization approach was used to explore the causal relationship between immune cells and the risk of inflammatory joint diseases.Methods A dataset of 731 immune cells and osteoarthritis,ankylosing spondylitis,gout,and psoriatic arthritis was obtained from the Finngen database and the GWAS catalog database.The causal relationship between immune cells and osteoarthritis was explored using inverse variance weighting,weighted median and MR-Egger methods,and the stability and reliability of the research results were evaluated using Cochran′s Q test,MR-Egger regression,MR-PRESSO,Leave one out method,and Meta-analysis.Results A total of 45 immune cells were obtained with osteoarthritis,35 immune cells with ankylosing spondylitis,29 immune cells with gout,and 36 immune cells with psoriatic arthritis in a potential causal relationship(P<0.05).There was a significant causal relationship between HLA DR on CD14-CD16+monocyte and ankylosing spondylitis(P<6.8×10^(-5)),and the results were stable,but Meta-analysis showed that the causal relationship was not significant(OR=1.00,95%CI:1.00-1.00).Conclusion This study preliminarily reveals the causal relationship between immune cells and inflammatory joint diseases represented by ankylosing spondylitis from the perspective of genetics,and provides an important theoretical basis for future precision medicine and individualized treatment.