Journal of Molecular Medicine

, Volume 95, Issue 12, pp 1269–1282 | Cite as

High-altitude adaptation in humans: from genomics to integrative physiology

  • Priti Azad
  • Tsering Stobdan
  • Dan Zhou
  • Iain Hartley
  • Ali Akbari
  • Vineet Bafna
  • Gabriel G HaddadEmail author


About 1.2 to 33% of high-altitude populations suffer from Monge’s disease or chronic mountain sickness (CMS). Number of factors such as age, sex, and population of origin (older, male, Andean) contribute to the percentage reported from a variety of samples. It is estimated that there are around 83 million people who live at altitudes > 2500 m worldwide and are at risk for CMS. In this review, we focus on a human “experiment in nature” in various high-altitude locations in the world—namely, Andean, Tibetan, and Ethiopian populations that have lived under chronic hypoxia conditions for thousands of years. We discuss the adaptive as well as mal-adaptive changes at the genomic and physiological levels. Although different genes seem to be involved in adaptation in the three populations, we can observe convergence at genetic and signaling, as well as physiological levels. What is important is that we and others have shown that lessons learned from the genes mined at high altitude can be helpful in better understanding and treating diseases that occur at sea level. We discuss two such examples: EDNRB and SENP1 and their role in cardiac tolerance and in the polycythemic response, respectively.


High-altitude adaptation Chronic mountain sickness Genomics Polycythemic response Cardiovascular response 



Our study is funded by NIH grant 1P01HL098053 and 5P01HD32573 to GGH, VB, and AA who were supported in part by grants from the NSF (DBI-1458557, IIS-1318386) and NIH (1R01GM114362). Dr. Vineet Bafna is a co-founder, has an equity interest, and receives income from Digital Proteomics, LLC. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. DP was not involved in the research presented here. The authors declare no competing financial interests.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Priti Azad
    • 1
  • Tsering Stobdan
    • 1
  • Dan Zhou
    • 1
  • Iain Hartley
    • 1
  • Ali Akbari
    • 2
  • Vineet Bafna
    • 2
  • Gabriel G Haddad
    • 1
    • 3
    • 4
    Email author
  1. 1.Division of Respiratory Medicine, Department of PediatricsUniversity of California San DiegoLa JollaUSA
  2. 2.Department of Computer Science and EngineeringUniversity of California San DiegoLa JollaUSA
  3. 3.Department of NeurosciencesUniversity of California San DiegoLa JollaUSA
  4. 4.Rady Children’s HospitalSan DiegoUSA

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