南方医科大学学报2025，Vol.45Issue(4)：871-879,9.DOI:10.12122/j.issn.1673-4254.2025.04.23
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
摘要
Abstract
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 leave-one-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Key words
Mendelian randomization/causal association/autoimmune diseases/aplastic anemia引用本文复制引用
李文婕,洪耀南,黄蕊,李煜宸,张莹,张蕴,吴迪炯..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[J].南方医科大学学报,2025,45(4):871-879,9.基金项目
国家自然科学基金(82174138) （82174138）
浙江省卫生健康科技计划(2022RC216) （2022RC216）
浙江省名老中医专家传承工作室建设项目(GZS2021022) Supported by National Natural Science Foundation of China(82174138). （GZS2021022）
