Causal relationship between type 1 diabetes and ovarian cancer:a Mendelian randomization study
Objective To assess the bidirectional causality between type 1 diabetes mellitus(T1DM)and ovarian cancer(OC).Methods Gene variants for T1DM(9 266 European ancestry patients and 15 574 controls)and OC(1 218 European ancestry patients and 198 523 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=1.000 4,95%CI 1.000 1-1.000 8,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 3.09×10-5-3.16×104,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.
type 1 diabetesovarian cancergenome-wide association studyMendelian randomizationcausal relationship
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