Genetic signatures of high-altitude adaptation in Tibetans

Jian Yang, Zi-Bing Jin, Jie Chen, Xiu-Feng Huang, Xiao-Man Li, Yuan-Bo Liang, Jian-Yang Mao, Xin Chen, Zhili Zheng, Andrew Bakshi, Dong-Dong Zheng, Mei-Qin Zheng, Naomi R Wray, Peter M Visscher, Fan Lu, Jia Qu

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44 Citations (Scopus)

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences
Early online date03 Apr 2017
DOIs
Publication statusEarly online date - 03 Apr 2017

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    Yang, J., Jin, Z-B., Chen, J., Huang, X-F., Li, X-M., Liang, Y-B., Mao, J-Y., Chen, X., Zheng, Z., Bakshi, A., Zheng, D-D., Zheng, M-Q., Wray, N. R., Visscher, P. M., Lu, F., & Qu, J. (2017). Genetic signatures of high-altitude adaptation in Tibetans. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1617042114