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

Hikmat Omolara SULAYMAN, Emmanuel Eze, Mariam Hussain, Aiman Khan, Barbara Guinn
2026 · doi:10.5281/zenodo.18635410 · W7128815018
Systematic review / meta-analysis OA: green CC0
Full text JSON View on OpenAlex View at publisher
⚙ AI-generated deep summary by qwen3.7-flash, 2026-09-20 · read from full text ⓘ

This systematic review and meta-analysis examined genetic factors associated with the development and progression of endometriosis in women of reproductive age. The authors analyzed 44 case-control studies involving over 70,000 participants, finding a significant association between specific genetic variants and disease risk with a pooled odds ratio of 1.50. Gene expression analysis revealed heterogeneous dysregulation across multiple studies, while functional enrichment highlighted inflammation, cellular stress responses, and growth-factor pathways as central to pathophysiology. This paper is centrally about endometriosis, focusing on the identification of heritable susceptibility factors and potential therapeutic targets through genetic association studies.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

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.
Full text 4,117 characters · extracted from oa-doi-fallback · 2 sections · click to expand

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. Files Suppl Info 1 Protocol.pdf Files (12.4 MB) | Name | Size | Download all | |---|---|---| | md5:0c9d2be5f902106e4451358c92ef1499 | 8.5 kB | Download | | md5:3e5feac53ab8b59dad995fd553cf74c2 | 187.2 kB | Preview Download | | md5:a9548bc9739095c975374ab57b33991d | 50.2 kB | Download | | md5:11443c55a11bf59d07aa85fc31beb95f | 23.9 kB | Preview Download | | md5:947c09ffc5eb5c372cfaa83015fcb736 | 8.3 kB | Download | | md5:70add236b5304fe3858a2223578ba830 | 48.6 kB | Preview Download | | md5:f8958cada7001913b8e4a1d414ad8897 | 335.5 kB | Preview Download | | md5:653498374839bf0849bdabc58e6b8373 | 9.3 kB | Preview Download | | md5:ff8003c47d2bbae5d0ae6ac21cdb9bd7 | 11.4 kB | Download | | md5:56ff9e45bea4fb11466928a7fe0d26f0 | 2.3 MB | Download | | md5:4bc8a62dce80813b0499f0b43bfdca36 | 316.6 kB | Download | | md5:316869b90091112b2655207bac40af6b | 2.2 MB | Download | | md5:1b22d7b9bb8a34bbbe9bc2236f43afd6 | 20.3 kB | Download | | md5:a3d04c424714bbc6a838c123f7a92092 | 6.3 MB | Download | | md5:de1129a7ad249786f4b2e60d24b701bf | 313.9 kB | Download | | md5:29126cdf3128afb98bceb9edb73392b6 | 39.7 kB | Download | | md5:b0191351d6eb1708bcfb574d960d7694 | 58.5 kB | Download | | md5:940992a3847551cada0dc2875e0a37e5 | 65.8 kB | Preview Download | | md5:557fa78468c56045d47ba9e3494c0fd6 | 16.7 kB | Download | | md5:1b62942398caace0669a023fb18066fe | 5.0 kB | Preview Download | | md5:bb40c2e479fe8f7fa15ab6ce4d2b5414 | 8.7 kB | Preview Download | | md5:a59d50fcf0e0733ad88b91d0839c65df | 8.7 kB | Download | Additional details Dates - Available - 2026-02-13Supplementary data

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisadenomyosis

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

openalex
last seen: 2026-06-04T00:00:01.174412+00:00
License: CC0 · commercial use OK