ArticleAmerican journal of human genetics2018
An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Immunology of Normal Pregnancy and Preeclampsia and the Role of Placental Non-Classical HLA and Decidual NK Cells.International journal of molecular sciences · 2026Review
- Article
- HLA-F regulates the proliferation of trophoblast via PKM2-dependent glycolysis in the pathogenesis of preeclampsia.Molecular medicine (Cambridge, Mass.) · 2025Article
- Data-driven projections of candidate enhancer-activating SNPs in immune regulation.BMC genomics · 2025Article
- Emerging roles of natural killer cell ligands-HLA-E, HLA-F, HLA-G, MICA, and MICB-inFrontiers in genetics · 2025Review
- A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.American journal of human genetics · 2024Article
- The Long Non-Coding RNA GeneCells · 2024Article
- Cell Chirality of Micropatterned Endometrial Microvascular Endothelial Cells.Advanced healthcare materials · 2024Article
- Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia.Frontiers in immunology · 2023Article
- Narrative review of the relationship between the maternal-fetal interface immune tolerance and the onset of preeclampsia.Annals of translational medicine · 2022Review
- The role of extravillous trophoblasts and uterine NK cells in vascular remodeling during pregnancy.Frontiers in immunology · 2022Review
- A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker.Nature communications · 2021Article
- Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese.Journal of hepatocellular carcinoma · 2021Article
- Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth.Science advances · 2020Article
- Molecular mechanism for the multiple sclerosis risk variant rs17594362.Human molecular genetics · 2019Article
- A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion.Interface focus · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Variation in female reproductive traits, such as fertility, fecundity, and fecundability, are heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits have been challenging. Here, we explore the functional significance and evolutionary history of a G/A polymorphism at SNP rs2523393, which is an eQTL for HLA-F and is significantly associated with fecundability (the probability of being pregnant within a single menstrual cycle). We replicated the association between the rs2523393 genotype and HLA-F expression by using GTEx data and demonstrate that HLA-F is upregulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. Next, we show that the rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. Remarkably, we found that the A allele is derived in the human lineage and that the G/A polymorphism arose before the divergence of modern and archaic humans and segregates at intermediate to high frequencies across human populations. Remarkably, the derived A allele is has also been identified in a GWAS as a risk allele for multiple sclerosis. These data suggest that the polymorphism is maintained by antagonistic pleiotropy and a reproduction-health tradeoff in human evolution.
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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.