ArticleNature communications2024
A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 9 citations in OpenAlex.
- The importance of gene polymorphism in familial inheritance of endometriosis.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations.Nature genetics · 2026Article
- Evolutionary perspectives on endometrial cancer: antagonistic pleiotropy.Molecular & cellular oncology · 2026Review
- Immune-nutritional interactions in endometriosis: current evidence and future perspectives in disease management.Frontiers in immunology · 2026Review
- Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth.medRxiv : the preprint server for health sciences · 2025Article
- Parity modifies the effect of genetic variants associated with gestational duration and birth weight.medRxiv : the preprint server for health sciences · 2025Article
- Ping-Chong-Jiang-Ni Formula effectively inhibits migration and invasion of endometriosis 12Z cell line via TRIP13.Journal of food and drug analysis · 2025Article
- Research trends and hotspots of single nucleotide polymorphisms in endometrial cancer: a bibliometric analysis.Discover oncology · 2025Article
- Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.Nature medicine · 2025Article
- Pathogenesis of Endometriosis and Endometriosis-Associated Cancers.International journal of molecular sciences · 2024Review
- m6A methylation profiling as a prognostic marker in nasopharyngeal carcinoma: insights from MeRIP-Seq and RNA-Seq.Frontiers in immunology · 2024Article
- A Common Genetic Factor Underlies Genetic Risk for Gynaecological and Reproductive Disorders and Is Correlated with Risk to Depression.Neuroendocrinology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
The common human SNP rs3820282 is associated with multiple phenotypes including gestational length and likelihood of endometriosis and cancer, presenting a paradigmatic pleiotropic variant. Deleterious pleiotropic mutations cause the co-occurrence of disorders either within individuals, or across population. When adverse and advantageous effects are combined, pleiotropy can maintain high population frequencies of deleterious alleles. To reveal the causal molecular mechanisms of this pleiotropic SNP, we introduced this substitution into the mouse genome by CRISPR/Cas 9. Previous work showed that rs3820282 introduces a high-affinity estrogen receptor alpha-binding site at the Wnt4 locus. Here, we show that this mutation upregulates Wnt4 transcription in endometrial stroma, following the preovulatory estrogen peak. Effects on uterine transcription include downregulation of epithelial proliferation and induction of progesterone-regulated pro-implantation genes. We propose that these changes increase uterine permissiveness to embryo invasion, whereas they decrease resistance to invasion by cancer and endometriotic foci in other estrogen-responsive tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.