Ainash Childebayeva

AINASH CHILDEBAYEVA, then a graduate student at University of Michigan, Ann Arbor, Michigan, was awarded a grant in October 2017 to aid research on “Epigenetic Signatures of High-Altitude Adaptation,” supervised by Dr. Abigail Bigham. High-altitude adaptation is a classic example of natural selection operating on the human genome. Physiological and genetic adaptations have been documented in populations with a history of living at high altitude. However, the role of the epigenetic gene regulation (including DNA methylation) in high-altitude adaptation is not well understood. The research focuses on the Andean Quechua to determine what epigenetic factors are associated with high-altitude adaptation and high-altitude adaptive phenotypes. An epigenome-wide DNA methylation study was performed in Peruvian Quechua with differential lifetime exposures to high altitude. The study identified significant differentially methylated positions (DMPs) and differentially methylated regions (DMRs) associated with high-altitude developmental and lifelong exposures. These positions and regions are associated with hypoxia-inducible factor pathway, red blood cell production, blood pressure, and others. DMPs and DMRs associated with exhaled Fractional exhaled Nitric Oxide (FeNO) were also identified. Based on a GWAS in a larger cohort of Peruvian Quechua, a significant association between EPAS1 methylation and EPAS1 SNPs was found. Results also show that EPAS1 methylation mediates the relationship between altitude acclimatization and hemoglobin. Lastly, research found that individuals with the longest lifetime exposure to high altitude showed accelerated epigenetic aging compared to participants born at low altitude.