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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.

Original publication

DOI

10.1073/pnas.1617042114

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

04/2017

Volume

114

Pages

4189 - 4194

Addresses

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.

Keywords

Humans, Genetic Markers, Altitude, Adaptation, Physiological, Phenotype, Alleles, Tibet, Female, Male, Genome-Wide Association Study, Selection, Genetic, Ethnicity