自身免疫性疾病是再生障碍性贫血的危险因素:一项孟德尔随机化分析  

Causal relationship between autoimmune diseases and aplastic anemia:A Mendelian randomization study

作　　者：李文婕 洪耀南 黄蕊 李煜宸 张莹[1] 张蕴[1,2,3] 吴迪炯 LI Wenjie;HONG Yaonan;HUANG Rui;LI Yuchen;ZHANG Ying;ZHANG Yun;WU Dijiong(First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,China;First School of Clinical Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China;National Traditional Chinese Medicine Clinical Research Base of Hematology,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学附属第一医院//浙江省中医院,浙江杭州310006 [2]浙江中医药大学附属第一临床医学院,浙江杭州310053 [3]国家中医(血液病)临床研究基地,浙江杭州310053

出　　处：《南方医科大学学报》2025年第4期871-879,共9页Journal of Southern Medical University

基　　金：国家自然科学基金(82174138);浙江省卫生健康科技计划(2022RC216);浙江省名老中医专家传承工作室建设项目(GZS2021022)。

摘　　要：目的采用孟德尔随机化分析来探讨10种自身免疫性疾病(ADs)与再生障碍性贫血(AA)之间的因果关联。方法利用公开的全基因组关联研究数据获取ADs与AA的单核苷酸多态性(SNPs)并进行分析。以逆方差加权法(IVW)为主要分析方法,MR Egger法、Weighted Mode法、Weighted median法、Simple Mode法则作为补充分析。使用heterogeneity函数和pleiotropy函数等分别进行异质性检验和水平多效性分析,采用留一法评估孟德尔随机化分析结果的稳健性。结果两样本孟德尔随机化的IVW法分析显示,类风湿性关节炎(OR=1.094,95%CI:1.023-1.170,P=0.009,P.adjust=0.042)、系统性红斑狼疮(OR=1.111,95%CI:1.021-1.208,P=0.015,P.adjust=0.036)、桥本甲状腺炎(OR=1.206,95%CI:1.049-1.387,P=0.009,P.adjust=0.029)和干燥综合征(OR=1.173,95%CI:1.054-1.306,P=0.004,P.adjust=0.035)与再生障碍性贫血呈显著正向因果关联,Weighted median法等分析结果同样支持以上结果。敏感性分析显示不存在水平多效性和异质性,留一法显示因果关系稳健。未发现格雷夫斯病、溃疡性结肠炎、克罗恩病、自身免疫性肝炎、原发性胆汁性胆管炎和原发性硬化性胆管炎与AA发病直接相关的证据(P>0.05,P.adjust>0.05),与AA不存在因果关联。反向孟德尔随机化结果及多重校正显示,AA不是ADs(P.adjust>0.05)的影响因素。结论本研究在基因水平上支持类风湿性关节炎、系统性红斑狼疮、桥本甲状腺炎和干燥综合征是再生障碍性贫血的危险因素,证实了这4种ADs在增加AA风险方面存在因果关系。Objective To investigate the causal associations between autoimmune diseases and aplastic anemia(AA)using Mendelian randomization analysis.Methods Publicly available genome-wide association study(GWAS)data were utilized to obtain single nucleotide polymorphisms(SNPs)associated with autoimmune diseases and AA for analysis.The inverse variance weighted(IVW)method was employed as the primary analytical approach,with MR Egger,Weighted Mode,Weighted Median,and Simple Mode methods serving as complementary analyses.Heterogeneity and pleiotropy analyses were conducted using designated functions,and the robustness of Mendelian randomization results was assessed using leaveone-out analysis.Results The two-sample Mendelian randomization analysis using the IVW method revealed significant positive causal associations of rheumatoid arthritis(OR=1.094,95%CI:1.023-1.170,P=0.009,adjusted P=0.042),systemic lupus erythematosus(OR=1.111,95%CI:1.021-1.208,P=0.015,adjusted P=0.036),Hashimoto thyroiditis(OR=1.206,95%CI:1.049-1.387,P=0.009,adjusted P=0.029),and Sicca syndrome(OR=1.173,95%CI:1.054-1.306,P=0.004,adjusted P=0.035)with AA,which was supported by the results from the Weighted Median method.Sensitivity analyses indicated no evidence of pleiotropy or heterogeneity,and leave-one-out analysis confirmed the robustness of the causal relationships.No direct evidence was found linking Graves'disease,ulcerative colitis,Crohn's disease,autoimmune hepatitis,primary biliary cholangitis,or primary sclerosing cholangitis with AA(P>0.05,adjusted P>0.05),indicating a lack of causal association.Reverse Mendelian randomization results and multiple corrections indicated that AA was not an influencing factor for autoimmune diseases(adjusted P>0.05).Conclusion Our findings support at the genetic level that rheumatoid arthritis,systemic lupus erythematosus,Hashimoto thyroiditis,and Sicca syndrome are risk factors for AA,and confirm a causal association of the these 4 autoimmune diseases with an increased risk of AA.

关 键 词：孟德尔随机化 因果关联 自身免疫性疾病 再生障碍性贫血 

分 类 号：R556[医药卫生—血液循环系统疾病]