Genetic signatures of high-altitude adaptation in Tibetans

Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):4189-4194. doi: 10.1073/pnas.1617042114. Epub 2017 Apr 3.


Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase (MTHFR) and EPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the MTHFR locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans.

Keywords: Tibetans; genome-wide association study; high-altitude adaptation; mixed linear model; polygenic selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Alleles
  • Altitude*
  • Ethnic Groups / genetics*
  • Female
  • Genetic Markers*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Phenotype
  • Selection, Genetic*
  • Tibet


  • Genetic Markers