1型糖尿病与卵巢癌之间的因果关系:一项孟德尔随机化研究  

Causal relationship between type 1 diabetes and ovarian cancer:a Mendelian randomization study

作　　者：张玲[1] 吴媛霞[2] 乔翠峰[1] 杜秀萍[1] ZHANG Ling;WU Yuanxia;QIAO Cuifeng;DU Xiuping(Department of Gynaecology and Obstetrics,Shanxi Maternal and Child Health Hospital,Taiyuan 030012,China;Medical Reproductive Center,Shanxi Maternal and Child Health Hospital)

机构地区：[1]山西省妇幼保健院妇产科,太原030012 [2]山西省妇幼保健院医学生殖中心

出　　处：《山西医科大学学报》2024年第9期1122-1126,共5页Journal of Shanxi Medical University

摘　　要：目的 探计1型糖尿病(type 1 diabetes,T1DM)和卵巢癌(ovarian cancer,OC)之间的双向因果关系。方法 采用两样本孟德尔随机化(MR)设计,使用来自全基因组关联研究(GWAS)的T1DM遗传变异(9 266例欧洲血统病例和15 574例对照)和OC遗传变异(1 218例欧洲血统病例和198 523例对照)。采用MR-Egger、加权中位数(WME)、逆方差加权法(IVW)、简单模式(simple mode)和加权模式(weighted mode)来检验T1DM与OC之间的因果关系。然后采用留一法(leave-one-out)等敏感度分析来评估结果的可靠性。最后采用MR Steiger检验来测试暴露和结果之间的假设关系。结果 IVW法结果显示T1DM与OC的发病率增高有因果关系(OR=1.000 4,95%CI 1.000 1~1.000 8,P=9.01×10^(-3)),5种方法的估计值在方向上保持一致,表明T1DM是OC发病率的危险因素。MR Egger模型证实了结果无显著异质性(P>0.05),留一法敏感性分析去除单个SNP并重复进行MR分析时,结果较前无显著差异。Egger截距接近于零(截距<-0.001,P=0.191),表明本研究无水平多效性。同时反向MR分析并未发现OC促进T1DM发病风险增高的证据(OR=0.988,95%CI 3.09×10^(-5)~3.16×10^(4),P=0.998)。结论 遗传学证据表明,T1DM与OC的发病风险增加有关,相反,并未发现OC会使T1DM发病风险增高。Objective To assess the bidirectional causality between type 1 diabetes mellitus(T1DM)and ovarian cancer(OC).Methods Gene variants for T1DM(9266 European ancestry patients and 15574 controls)and OC(1218 European ancestry patients and 198523 controls)from genome-wide association studies(GWAS)were used in a two-sample Mendelian randomization(MR)design.MR-Egger,weighted median(WME),inverse variance weighting(IVW),simple mode and weighted mode were used to test the causal relationship between T1DM and OC.Leave-one-out sensitivity analysis was used to assess the reliability of the results.Finally,MR Steiger test was used to test the hypothesized relationship between exposure and outcome.Results The results of IVW showed a causal relationship between T1DM and the incidence of OC(OR=1.0004,95%CI 1.0001-1.0008,P=9.01×10^(-3)),and the estimates of the above five methods were consistent in direction,indicating that T1DM was a risk factor for the incidence of OC.The MR Egger model confirmed that there was no significant heterogeneity in the results(P>0.05).There was no significant difference in the results when a single SNP was removed from the sensitivity analysis and the repeated MR analysis was carried out.The Egger intercept was close to zero(intercept<-0.001,P=0.191),indicating that there was no horizontal pleiotropy in this study.Meanwhile,reverse MR analysis did not show any evidence that OC increased the risk of T1DM(OR=0.988,95%CI 3.09×10^(-5)-3.16×10^(4),P=0.998).Conclu-sion Genetic evidence shows that T1DM can be associated with the OC risk increase,while OC can not increase the risk of T1DM.

关 键 词：1型糖尿病 卵巢癌 全基因组关联研究 孟德尔随机化 因果关系 

分 类 号：R737.31[医药卫生—肿瘤]