多囊卵巢综合征生物学标志物探索:孟德尔随机化和共定位分析  

Exploring biological markers of PCOS:Mendelian randomization and colocalization analysis

作　　者：凌少华 覃晓[2] 田纯 黄利营 李丽宁 覃莉[1] LING Shao-hua;QIN Xiao;TIAN Chun;HUANG Li-ying;LI Li-ning;QIN Li(The Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000;The People’s Hospital of Baise,Baise 533000)

机构地区：[1]右江民族医学院附属医院,百色533000 [2]百色市人民医院,百色533000

出　　处：《生殖医学杂志》2024年第12期1644-1649,共6页Journal of Reproductive Medicine

基　　金：广西青年科学基金(2019GXNSFBA245020);右江民族医学院附属医院高层次人才科研项目(Y20196316)。

摘　　要：目的 采用基于汇总数据的孟德尔随机化(SMR)和共定位分析,整合多组学数据来探索与PCOS发病风险相关的生物学标记物。方法 基因表达和蛋白质丰度的遗传汇总数据分别来自GTEx/eQTLGen数据库和Ferkingstad等的研究,PCOS的全基因组关联分析(GWAS)数据来自FinnGen和UKB数据库,采用SMR分析来评估基因/蛋白质与PCOS发病风险之间的因果关系,并对候选基因进行共定位分析以进一步探索基因/蛋白与PCOS之间潜在的共同因果变异。结果 SMR分析结果发现,共有323个基因、26个蛋白与PCOS发病风险相关(Pvalue<0.01,PHEIDI>0.05),其中有7个基因在蛋白丰度和基因表达层面都与PCOS发病风险相关,结合共定位分析结果,共得到4个基因在基因表达和蛋白丰度层面均与PCOS发病风险相关,且具有中高水平证据的共定位。在蛋白丰度层面上,ATP1B2[OR=1.274,95%CI(1.091,1.487)]的高表达与PCOS发病风险增加相关,而ATOX1[OR=0.345,95%CI(0.169,0.704)]、RIDA[OR=0.730,95%CI(0.613,0.869)]和STX8[OR=0.291,95%CI(0.123,0.689)]的低表达与PCOS发病风险增加相关。结论 ATOX1、ATP1B2、RIDA和STX8可能与PCOS发病存在因果关系。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(P value<0.01,P HEIDI>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.

关 键 词：多囊卵巢综合征 孟德尔随机化分析 共定位分析 QTL 

分 类 号：R711.6[医药卫生—妇产科学]