The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

BMC Medicine

Research Article

Shuting Ye¹  Bumei Zhang¹  Yan Li¹  Hongyan Liu¹  Xiaopei Li¹  Yongrui Du¹  Jianmei Wang¹  Yang Yang²  Jiapei Yuan³ 

[1] Department of Family Planning, The Second Hospital of Tianjin Medical University, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;Department of Family Planning, The Second Hospital of Tianjin Medical University, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China;State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystems, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 300020, Tianjin, China;

关键词: Two-sample Mendelian randomization;    Endometriosis;    Coagulation;    GWAS;    ADAMTS13;   

DOI  :  10.1186/s12916-023-02881-z

 received in 2023-01-20, accepted in 2023-04-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEndometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis.MethodsTo investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis.ResultsOur two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses.ConclusionsOur MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2023_36_Article_IEq7.gif

41116_2023_36_Article_IEq6.gif

41116_2023_36_Article_IEq4.gif

41116_2023_36_Article_IEq2.gif

Fig. 2

Fig. 4