The Genetic Basis of Endometriosis: Evidence from a Systematic Review and MetaAnalysis

Objectives: To examine the genetic factors associated with the development and progression of endometriosis. To gain insight into how these factors influence disease susceptibility among women with similar risk profiles, enhance risk stratification, improve the potential for personalized treatment, and identify new therapeutic targets. Evidence Review: The systematic review was conducted using PubMed, the Cochrane Library, Scopus, Medline (via EBSCO), CINAHL Ultimate (via EBSCO), and Google Scholar. The review included primary case-control studies that examined genetic traits, gene mutations, gene expression patterns, or inheritance patterns associated with endometriosis in women of reproductive age (15-49 years) from inception to 20 March 2025. Studies were excluded if they involved animal models, cell lines, adenomyosis, ovarian cancer, drugs, or addressed issues not linked to genetics or inheritance patterns. In addition, case reports, reviews, systematic reviews, and meta-analyses were excluded. Two independent reviewers, working autonomously, performed study screening and eligibility assessment to ensure an objective and thorough process. The Modified Newcastle-Ottawa Scale was used to assess the risk of bias. A total of 44 studies were included in the meta-analysis examining the association between genetic variants and 25,347 endometriosis patients compared with 47,312 controls. Data synthesis was carried out using a combination of random-effects meta-analysis, narrative synthesis, and functional enrichment analysis. Results: Fifty-two studies were included in the analysis of genetic variants and gene expression patterns. Meta-analysis of genetic variant studies (n=44) showed a significant association with endometriosis risk, with a pooled odds ratio of 1.50 (95% confidence interval (CI) 1.22–1.86; I² = 82.1%). Quantitative synthesis of the gene expression studies (n=8) yielded an overall effect estimate of standardised mean difference (SMD) of 0.78 (95% confidence interval (CI) −3.49 to 5.05; I² = 98.4%). Analysis indicated gene expression was heterogeneous, with qualitative assessment showing a wide range of genes recurrently dysregulated across studies. Functional pathway analysis highlighted extracellular signalling, inflammation, cellular stress responses, and growth-factor-dependent pathways as central processes implicated in the pathophysiology of endometriosis.