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

Genetic signatures of high-altitude adaptation in Tibetans.

Author information

1
Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; jqu@mail.eye.ac.cn lufan@mail.eye.ac.cn jinzb@mail.eye.ac.cn jian.yang@uq.edu.au.
2
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, China National Engineering Research Center of Ophthalmology and Optometry, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou 325027, China.
3
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, China National Engineering Research Center of Ophthalmology and Optometry, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou 325027, China jqu@mail.eye.ac.cn lufan@mail.eye.ac.cn jinzb@mail.eye.ac.cn jian.yang@uq.edu.au.
4
Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.

Abstract

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

PMID:
28373541
PMCID:
PMC5402460
DOI:
10.1073/pnas.1617042114
[Indexed for MEDLINE]
Free PMC Article

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