口腔疾病防治2025，Vol.33Issue(4)：296-304,9.DOI:10.12016/j.issn.2096-1456.202440381
双向孟德尔随机化分析免疫细胞表型与复发性阿弗他溃疡之间的因果关系
Bidirectional Mendelian randomization analysis of causal relationships between immune cell traits and recur-rent aphthous ulceration
摘要
Abstract
Objective To explore the bidirectional causal relationship between 731 immune cell phenotypes and re-current aphthous ulcers(RAU)using Mendelian randomization(MR).Methods A two-sample bidirectional MR study was conducted using publicly available genome-wide association study(GWAS)summary statistics for 731 immune cell phenotypes and the RAU GWAS summary data from the FinnGen consortium.The inverse-variance weighted(IVW)method was used as the primary analysis tool,with supplementary analyses including the weighted median(WM)meth-od,MR-Egger regression,weighted mode,and simple mode.Sensitivity analyses were conducted using Cochran’s Q test,the mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)method for detecting pleiotropy and outliers,and leave-one-out cross-validation.Furthermore,differential analysis was performed using a clinical cohort dataset from the Gene Expression Omnibus(GEO)to further validate the MR results.Results In the forward MR anal-ysis,731 immune cell phenotypes were considered as exposures and RAU as the outcome.Among them,52 immune cell phenotypes showed a significant causal effect on RAU(P＜0.05).After false discovery rate(FDR)correction,two im-mune phenotypes remained significantly associated with RAU risk:with increased monocyte-derived myeloid suppressor cells(M-MDSC)(OR=1.06;95%CI:1.03-1.09)and CD33 on granulocytic myeloid-derived suppressor cells(G-MDSC)(OR=1.06;95%CI:1.03-1.09),the risk of RAU also increased.In reverse MR,RAU was found to have a significant causal effect on two immune cell phenotypes(P＜0.05),but no significant effects were found after FDR correction.Sen-sitivity analysis showed no significant heterogeneity between SNPs(P＞0.05).Differential analysis of the GEO dataset revealed that the characteristic genes of myeloid-derived suppressor cells(MDSC)(CTBS,IPMK,and UBA3)were signif-icantly upregulated in RAU(P＜0.05).Conclusion The MR results of 731 immune cell phenotypes suggest that M-MDSC and CD33 molecules on G-MDSC may be risk factors for RAU development.The clinical GEO dataset further validated that MDSC may play a role in RAU,while RAU did not show a significant causal association with the 731 im-mune cell phenotypes.关键词
免疫表型/复发性阿弗他溃疡/因果推断/孟德尔随机化/髓源性抑制细胞/单核髓源性抑制细胞/粒细胞髓源性抑制细胞/单核苷酸多态性/基因组关联研究分类
口腔医学引用本文复制引用
谢雪洁,徐隽,刘媛,陈悦,唐莉,古丽努尔·阿吾提..双向孟德尔随机化分析免疫细胞表型与复发性阿弗他溃疡之间的因果关系[J].口腔疾病防治,2025,33(4):296-304,9.基金项目
新疆维吾尔自治区青年科学基金(2022D01C253) This study was supported by the grants from The Youth Science Foundation of Xinjiang Uygur Autonomous Region(2022D01C253). （2022D01C253）
