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Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude.

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dc.contributor.author Brutsaert, Tom D.
dc.contributor.author Kiyamu, Melisa
dc.contributor.author Elias Revollendo, Gianpietro
dc.contributor.author Isherwood, Jenna L.
dc.contributor.author Lee, Frank S.
dc.contributor.author Rivera-Ch, Maria
dc.contributor.author Leon-Velarde, Fabiola
dc.contributor.author Ghosh, Sudipta
dc.contributor.author Bigham, Abigail W.
dc.date.accessioned 2019-12-06T21:02:54Z
dc.date.available 2019-12-06T21:02:54Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/7485
dc.description.abstract Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-alpha (HIF-alpha), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (Lmin(-1) and mLmin(-1)kg(-1)) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by approximately 11% (e.g., for rs1769793 SNP genotype TT = 34.2 mLmin(-1)kg(-1) vs. CC = 30.5 mLmin(-1)kg(-1)). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua. en_US
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartof urn:issn:1091-6490
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject aerobic capacity en_US
dc.subject evolution en_US
dc.subject hypoxia en_US
dc.subject Peruvian Quechua en_US
dc.subject selection en_US
dc.title Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1073/pnas.1906171116
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.02
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.11


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