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Coagulation factors may contribute to the risk of endometriosis development.
The results of the Mendelian randomization (MR) study revealed that there are causal connections between ADAMTS13/vWF and the risk of developing endometriosis. Yan Li et al. aimed to explore the potential causal link between coagulation factors and the likelihood of developing complex gynecological disorders. Their investigation employed a two-sample MR analytic framework to delve into this research question.
Rigorous quality control procedures were implemented to identify suitable instrumental variables that exhibited strong associations with the exposures [plasmin, protein C, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), endogenous thrombin potential (ETP), factor X (FX), factor VII (FVII), factor XI (FXI), factor VIII (FVIII), activated partial thromboplastin time (aPTT), and disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13)].
Notably, 2 independent cohorts of individuals with European ancestry, UK Biobank (comprising 4354 cases and 217,500 controls) and FinnGen (comprising 8288 cases and 68,969 controls), were utilized, making use of endometriosis Genome-wide association studies (GWAS) summary statistics. Followed by a meta-analysis, MR analyses were conducted separately in both cohorts. To evaluate horizontal pleiotropy, heterogeneity, and the stability of single nucleotide polymorphisms related to endometriosis, leave-one-out sensitivity analyses, MR-Egger intercept test, and Cochran's Q test were employed.
By conducting a two-sample MR analysis on 11 coagulation factors using data from the UK Biobank, it was found that genetically predicted plasma ADAMTS13 levels were associated with a declined risk of endometriosis, providing reliable evidence of a causal effect. Conversely, in the FinnGen cohort, a negative causal impact of ADAMTS13 was noted. Furthermore, a positive causal impact of vWF on endometriosis was witnessed. In the meta-analysis, these causal correlations remained significant and exhibited a strong effect size. Moreover, the MR analyses also unveiled potential causal effects of ADAMTS13 and vWF on various sub-phenotypes of endometriosis.
The MR analysis utilizing GWAS data from extensive population studies, the presence of causal connections between ADAMTS13/vWF and the risk of endometriosis has been established. These groundbreaking results not only elucidate the mechanisms underlying endometriosis but also open up exciting possibilities for therapeutic interventions. The implicated coagulation factors, ADAMTS13 and vWF, could serve as promising targets for the development of novel treatments, offering hope to millions of women grappling with the debilitating symptoms of endometriosis.
BMC Medicine
The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study
Yan Li et al.
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