ArticleNature genetics2014
A genetic mechanism for Tibetan high-altitude adaptation.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers, 2 of them syntheses that pooled it.
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Who cites it
244 citing papers in PubMed, 2 syntheses or guidelines pooled it, 430 citations in OpenAlex.
- Does intermittent exposure to high altitude increase the risk of cardiovascular disease in workers? A systematic narrative review.BMJ open · 2020Pooled it
- Combination of 247 Genome-Wide Association Studies Reveals High Cancer Risk as a Result of Evolutionary Adaptation.Molecular biology and evolution · 2018Pooled it
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Synergistic Effects of Diabetes, Inflammatory/Coagulopathy Biomarkers, TG and Hypoxic Stress on Premature Coronary Heart Disease in High-Altitude Populations.Journal of cardiovascular development and disease · 2026Article
- Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world's highest-dwelling mammal.Science (New York, N.Y.) · 2026Article
- Agentic AI in global health equity for high altitude populations.NPJ digital medicine · 2026Review
- Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?NPJ Parkinson's disease · 2026Review
- A Perturb-seq screen guided by species divergence uncovers pathways for collateral artery formation.bioRxiv : the preprint server for biology · 2026Article
- Effects of Continuous Low-dose Nitric Oxide in a Murine Model of Pulmonary Hypertension with Impaired Lung Development.Anesthesiology · 2026Article
- Hypoxic CA9 variant as a potential prognostic marker in gastric and breast cancers.Scientific reports · 2026Article
- DNA methylation-mediated regulation of hypoxia-responsive genes facilitates high-altitude adaptation in Tibetan chickens.Poultry science · 2026Article
- Human adaptation to high-altitude: A contemporary comparison of the oxygen cascade in Andean, Tibetan and Ethiopian highlanders.Experimental physiology · 2026Review
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- Demographics, clinical features, and comorbidities of high-altitude polycythaemia: a multicentre, retrospective, observational study.Journal of global health · 2026Observational
- Unlocking Ethiopia's genomic landscape and its global significance: a call for inclusive genomics research.Human genomics · 2026Review
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Mouse placentae generated by in vitro fertilization exhibit altered gene expression, activated hypoxia responses, and reduced fitness†.Biology of reproduction · 2026Article
- Mitochondrial retrograde signaling initiates HIF-1α/BNIP3/NIX-mediated mitophagy in Tibetan high-altitude adaptation.Cell death discovery · 2026Article
- Article
- High-altitude polycythemia: State-of-the-art review.Therapeutic advances in hematology · 2026Review
184 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 13 institutions in 4 countries.
Funding
Abstract
Tibetans do not exhibit increased hemoglobin concentration at high altitude. We describe a high-frequency missense mutation in the EGLN1 gene, which encodes prolyl hydroxylase 2 (PHD2), that contributes to this adaptive response. We show that a variant in EGLN1, c.[12C>G; 380G>C], contributes functionally to the Tibetan high-altitude phenotype. PHD2 triggers the degradation of hypoxia-inducible factors (HIFs), which mediate many physiological responses to hypoxia, including erythropoiesis. The PHD2 p.[Asp4Glu; Cys127Ser] variant exhibits a lower K(m) value for oxygen, suggesting that it promotes increased HIF degradation under hypoxic conditions. Whereas hypoxia stimulates the proliferation of wild-type erythroid progenitors, the proliferation of progenitors with the c.[12C>G; 380G>C] mutation in EGLN1 is significantly impaired under hypoxic culture conditions. We show that the c.[12C>G; 380G>C] mutation originated ∼8,000 years ago on the same haplotype previously associated with adaptation to high altitude. The c.[12C>G; 380G>C] mutation abrogates hypoxia-induced and HIF-mediated augmentation of erythropoiesis, which provides a molecular mechanism for the observed protection of Tibetans from polycythemia at high altitude.
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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.