Functional <i>EPAS1</i>/<i>HIF2A</i> missense variant is associated with hematocrit in Andean highlanders.

ABSTRACT: Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although th

SUBMITTER: Lawrence ES 

PROVIDER: S-EPMC10857371 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature