Objective:To explore the association of circulating inflammatory factors with PCOS at the genetic level with Mendelian randomization(MR).Methods:A genome-wide association study(GW AS)dataset of circulating inflammatory factors was obtained from the SCALLOP consortium database(https://www.phpc.cam.ac.uk/ceu/proteins)to screen for eligible single nucleotide polymorphisms(SNPs)as exposure variables,and SNPs associated with PCOS were obtained from the Finngen database(r9.finngen.fi/pheno/E4_PCOS)to use as endpoints for MR studies.We used inverse variance weighting(IVW)for the main analysis to assess the causal effect,with the MR-Egger method,weighted median method(WME),weighted mode(WM),and simple mode(SM)for supplementary causal analyses.The Cochran'Q test and MR-Egger intercept test were used for sensitivity analysis.Results:The IVW results showed an association between circulating inflammatory factors including interleukin(IL)-18,IL-6,matrix metalloproteinases(MMP)-10,interferon(IFN)-γ and the risk of developing PCOS at the genetic level in a European population.IL-18[OR=1.255,95％CI(1.002,1.572),P=0.048],IL-6[OR=1.434,95％CI(1.025,2.008),P=0.036]and MMP-10[OR=1.338,95％CI(1.058,1.693),P=0.015]were positively correlated with the prevalence of PCOS,and IFN-γ[OR=0.631,95％CI(0.441,0.902),P=0.012]was negatively correlated with the incidence of PCOS.The sensitivity analysis detected no heterogeneity or horizontal pleiotropy(P＞0.05),which indicated no bias in the results.The leave-one-out analysis suggested that the results were robust.Conclusions:The results of our analyses showed a correlation between the circulating inflammatory factors including IL-18,IL-6,and MMP-10 and an increased risk of PCOS prevalence,and a correlation between IFN-γ and a decreased risk of PCOS prevalence at the gene level in a European population.
关键词
多囊卵巢综合征/循环炎症因子/孟德尔随机化研究
Key words
PCOS/Circulating inflammatory factor/Mendelian randomization study
维普
万方数据