Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality

Emmanuel O Adewuyi, Divya Mehta, Yadav Sapkota, International Endogene Consortium, 23andMe Research Team, Asa Auta, Kosuke Yoshihara, Valgerður Steinthórsdóttir, Andrew P. Morris, Mette Nyegaard, Lyn R Griffiths, Amelie Fassbender, Grant W Montgomery, Nilüfer Rahmioğlu, Immaculata De Vivo, Daniel I Chasman, Dale R Nyholt, Julie E. Buring, Futao Zhang, Todd L. Edwards, Sarah Jones, Dorien, Daniëlle Peterse, Kathryn M. Rexrode, Paul M. Ridker, Andrew J. Schork, Stuart MacGregor, Nicholas G. Martin, Christian M. Becker, Sosuke Adachi, Takayuki Enomoto, Atsushi Takahashi, Yoichiro Kamatani, Koichi Matsuda, Michiaki Kubo, Guðmar Þorleifsson, Reynir Tómas Geirsson, Unnur Þorsteinsdóttir, Leanne Wallace, Jian Yang, Digna R. Velez Edwards, Siew‐Kee Low, Krina T. Zondervan, Stacey A. Missmer, Thomas D'Hooghe, Thomas D’Hooghe, Kāri Stefánsson, Joyce Y. Tung, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Vladimir Vacic, Catherine H. Wilson
Human genetics · 2020 · vol. 140(3) , pp. 529–552 · doi:10.1007/s00439-020-02223-6 · PMID:32959083 · W3087605373
article OA: green CC0 ⤵ 36 in-corpus citations
🔓 Open OA copy Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06+body, 2026-06-06 ⓘ

Genetic analysis of endometriosis and depression revealed shared loci and a causal link between depression and endometriosis, as well as links with gastric mucosa abnormalities.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 · read from full text ⓘ

The study used genome-wide association study data to examine genetic overlap and potential causal relationships between endometriosis and depression, applying SECA and linkage disequilibrium score regression to quantify shared genetics, followed by meta-analysis of 709,111 individuals to identify 20 independent genome-wide significant loci (eight novel). Mendelian randomization analyses indicated a causal effect of depression on endometriosis, and gene-based combined testing across both traits highlighted 22 genome-wide significant genes and enrichment of biological pathways including cell–cell adhesion, inositol phosphate metabolism, Hippo-Merlin signaling dysregulation, and gastric mucosa abnormality. Additional analyses reported evidence that endometriosis and depression were each causally associated with at least one abnormal condition of gastric mucosa, while the paper’s limitation is that these conclusions are derived from GWAS-based statistical genetics and rely on the assumptions of the methods used. This paper is centrally about endometriosis — it identifies shared genetic loci and proposes causal links between endometriosis and depression involving gastric mucosa abnormalities.

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

Full text 3,952 characters · extracted from oa-html · 2 sections · click to expand

Abstract

Evidence from observational studies indicates that endometriosis and depression often co-occur. However, conflicting evidence exists, and the etiology as well as biological mechanisms underlying their comorbidity remain unknown. Utilizing genome-wide association study (GWAS) data, we comprehensively assessed the relationship between endometriosis and depression. Single nucleotide polymorphism effect concordance analysis (SECA) found a significant genetic overlap between endometriosis and depression (PFsig-permuted = 9.99 × 10−4). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (rG = 0.27, P = 8.85 × 10−27). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P < 5 × 10−8), of which eight are novel. Mendelian randomization analysis (MR) suggests a causal effect of depression on endometriosis. Combining gene-based association results across endometriosis and depression GWAS, we identified 22 genes with a genome-wide significant Fisher’s combined P value (FCPgene < 2.75 × 10−6). Genes with a nominal gene-based association (Pgene < 0.05) were significantly enriched across endometriosis and depression (Pbinomial-test = 2.90 × 10−4). Also, genes overlapping the two traits at Pgene < 0.1 (Pbinomial-test = 1.31 × 10−5) were significantly enriched for the biological pathways ‘cell–cell adhesion’, ‘inositol phosphate metabolism’, ‘Hippo-Merlin signaling dysregulation’ and ‘gastric mucosa abnormality’. These results reveal a shared genetic etiology for endometriosis and depression. Indeed, additional analyses found evidence of a causal association between each of endometriosis and depression and at least one abnormal condition of gastric mucosa. Our study confirms the comorbidity of endometriosis and depression, implicates links with gastric mucosa abnormalities in their causal pathways and reveals potential therapeutic targets for further investigation.

Keywords

Genetic analysis, endometriosis, depression, shared loci, casual links, gastric mucosa abnormality Document Type Journal Article Date of Publication 9-21-2021 Publication Title Human Genetics Publisher Springer School School of Medical and Health Sciences / Centre for Precision Health RAS ID 36124 Funders National Health and Medical Research Council Funding information : https://doi.org/10.1007/s00439-020-02223-6 Grant Number NHMRC Number : 241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1026033, 1050208 Grant Link http://purl.org/au-research/grants/nhmrc/241944 http://purl.org/au-research/grants/nhmrc/339462 http://purl.org/au-research/grants/nhmrc/389927 http://purl.org/au-research/grants/nhmrc/389875 http://purl.org/au-research/grants/nhmrc/389891 http://purl.org/au-research/grants/nhmrc/389892 http://purl.org/au-research/grants/nhmrc/389938 http://purl.org/au-research/grants/nhmrc/443036 http://purl.org/au-research/grants/nhmrc/442915 http://purl.org/au-research/grants/nhmrc/442981 http://purl.org/au-research/grants/nhmrc/496610 http://purl.org/au-research/grants/nhmrc/496739 http://purl.org/au-research/grants/nhmrc/552485 http://purl.org/au-research/grants/nhmrc/552498 Comments This is a post-peer-review, pre-copyedit version of an article published in Human Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00439-020-02223-6 Adewuyi, E. O., Mehta, D., Sapkota, Y., Auta, A., Yoshihara, K., Nyegaard, M., ... Nyholt, D. R. (2021). Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. Human Genetics, 140(3), 529-552. Included in Life Sciences Commons, Medicine and Health Sciences Commons, Physical Sciences and Mathematics Commons, Psychology Commons

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-html ⓘ

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

mesh:D004715endometriosis

MeSH descriptors

Depression Endometriosis Gastric Mucosa Depression Endometriosis Female Gastric Mucosa Genetic Predisposition to Disease Genome-Wide Association Study Humans Linkage Disequilibrium Polymorphism, Single Nucleotide

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (100)

Cited by (36)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:21:42.008780+00:00
License: CC0 · commercial use OK