title: Genetic signatures of high-altitude adaptation in Tibetans.
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) andEPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at theMTHFRlocus 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.
authors.affiliation: 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.|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.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Zi-Bing
authors.identifier: 0000-0003-0515-698X
authors.initials: ZB
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yuan-Bo
authors.initials: YB
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.|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.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bakshi
authors.affiliation: 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.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Mei-Qin
authors.initials: MQ
authors.lastname: Zheng
authors.affiliation: Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.affiliation: Institute for Molecular Bioscience, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.affiliation: 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.
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
mesh_terms: D000222:Adaptation, Physiological; D000483:Alleles; D000531:Altitude; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010641:Phenotype; D012641:Selection, Genetic; D018609:Tibet
chemical_list: D005819:Genetic Markers
keywords: Tibetans; genome-wide association study; high-altitude adaptation; mixed linear model; polygenic selection