Exploring biological markers of PCOS:Mendelian randomization and colocalization analysis
Objective:To explore the biological markers associated with PCOS by integrating multi-omics based on summary-data-based MR(SMR)and colocalization analysis.Methods:The summary-level data of gene expression and protein abundance levels were obtained from the GTEx V8/eQTLGen consortium and the studies of Ferkingstad et al.,respectively.The genome-wide association analysis(GWAS)data for PCOS were sourced from two studies:the FinnGen study and the UK Biobank study.SMR analysis was employed to evaluate the correlation between genes/proteins and the risk of PCOS.Additionally,colocalization analysis was conducted to explore potential shared causal variants between the identified genes/proteins and PCOS.Results:The results of SMR analysis showed that a total of 323 genes were identified as being associated with the risk of PCOS at the gene expression level,and 26 proteins were identified as being associated with the risk of PCOS at the protein abundance level(Pvalue＜0.01,PHEIDI＞0.05).Among them,seven genes were correlated with the risk of PCOS at both the gene expression level and protein abundance level.Combined with the results of the colocalization analysis,a total of four genes were showed as being associated with the risk of PCOS at both gene expression and protein abundance levels with moderate to high levels of evidence of colocalization.At protein abundance level,it was genetically predicted higher level of ATP1B2[OR=1.274,95％CI(1.091,1.487)]was associated with an increased risk of PCOS,while lower levels of ATOX1[OR=0.345,95％CI(0.169,0.704)],RIDA[OR=0.730,95％CI(0.613,0.869)],and STX8[OR=0.291,95％CI(0.123,0.689)]were associated with an increased risk of PCOS.Conclusions:ATOX1,ATP1B2,RIDA,and STX8 may be associated with the risk of PCOS.
PCOSMendelian randomizationColocalization analysisQuantitative trait loci
万方数据
维普
