摘要
目的使用两样本双向孟德尔随机化(TSMR)作为研究方法,探索46种表型(包括15种血清阳性病例对照表型和31种定量抗体测量表型)与溃疡性结肠炎(UC)的因果关系。方法使用46种抗体血清数据,根据预设的阈值提取与46种抗体血清的相对丰度显著相关的单核苷酸多态性(SNP)作为工具变量。UC的汇总统计数据来自OPEN GWAS数据库(n=47745)。采用MR-Egger回归、加权中位数法(WME)、逆方差加权法(IVW)、简单模式法(SM)、加权众数法(WM)估算抗体水平与UC之间的因果关系,其中以IVW法为主,根据效应指标优势比(OR)和95%置信区间(CI)评估结果。结合敏感性分析、异质性检验、基因多效性检验和异常值检验(MR-PRESSO)等方法来验证结果的稳定性和可靠性,并通过反向孟德尔随机化(MR)再次进行因果关联研究。结果IVW结果显示,EB病毒EA-D抗体水平(OR=0.806,95%CI=0.693~0.939,P<0.01)、EB病毒EBNA-1抗体水平(OR=1.870,95%CI=1.480%~2.360%,P<0.0001)、抗多瘤病毒2 IgG血清阳性(OR=0.570,95%CI=0.435~0.746,P<0.0001)与UC有关,根据反向MR分析结果显示,UC对抗多瘤病毒2 IgG血清阳性存在因果影响,上述均未发现IVs存在基因多效性或显著异质性。结论EB病毒EBNA-1抗体水平与UC的发生风险呈正相关;而EB病毒EA-D抗体水平、抗多瘤病毒2 IgG血清阳性与UC的发生风险呈负相关,即为UC的保护因素。
Objective To explore the causal relationship between 46 phenotypes(including 15 seropositive case-control phenotypes and 31 quantitative antibody-measurement phenotypes)and ulcerative colitis(UC)using two-sample bidirectional Mendelian randomization(TSMR).Methods Single nucleotide polymorphisms(SNPs)significantly associated with the relative abundance of the 46 antibody sera were extracted as instrumental variables according to preset thresholds.Summary statistics for UC were obtained from the OPEN GWAS database(n=47745).MR-Egger regression,weighted median method(WME),inverse variance weighting(IVW),the simple mode method(SM),and weighted multitude method(WM)were used to estimate the causal relationship between antibody levels and UC,primarily using the IVW method.The results were assessed according to the effect indicator dominance ratios(OR)and 95%confidence intervals(CI).Sensitivity analysis,heterogeneity test,gene pleiotropy test,and outlier test(MR-PRESSO)were combined to verify the stability and reliability of the results,and the causal association study was performed again using reverse Mendelian randomization(MR).Results IVW results showed that Epstein-Barr(EB)virus EA-D antibody levels(OR=0.806,95%CI=0.693-0.939,P<0.01),Epstein-Barr virus EBNA-1 antibody levels(OR=1.870%,95%CI=1.480-2.360,P<0.0001),Anti-polyomavirus 2 IgG seropositivity(OR=0.570,95%CI=0.435-0.746,P<0.0001)were associated with UC.The inverse MR analysis revealed a causal effect on anti-polyomavirus 2 IgG seropositivity,and none of the above revealed genetic pleiotropy or significant heterogeneity of IVs.Conclusion EB virus EBNA-1 antibody levels are positively associated with the risk of UC,while EB virus EA-D antibody levels and anti-polyomavirus 2 IgG seropositivity are negatively associated with the risk of UC,indicating that they are protective factors for UC.
作者
曾译萱
李倪仁
邓丙英
谢湃
区日泓
陈磊
刘怡
Zeng Yixuan;Li Niren;Deng Bingying;Xie Pai;Ou Rihong;Chen Lei;Liu Yi(Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics,Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515;School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006)
出处
《安徽医科大学学报》
北大核心
2025年第6期1098-1104,共7页
Acta Universitatis Medicinalis Anhui
基金
广东省自然科学基金(编号:2023A1515011060)
广东省中医药局科研项目(编号:20251247)。
