Related Experiment Video
Updated: Sep 14, 2025
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
34.0K
Adaptive PRKAA1 variant in Andeans is associated with improved ventilation and sleep phenotypes
Elijah S Lawrence1, Wanjun Gu1,2, Mitchell C Kong1,3
1Department of Medicine, Division of Pulmonary, Critical Care, Sleep Medicine, and Physiology University of California, San Diego, La Jolla, CA, USA.
Iscience
|July 24, 2025
Summary
Highlanders adapted to low oxygen with genetic changes in PRKAA1, an enzyme linked to breathing and sleep. A specific variant may improve breathing in low oxygen and protect against sleep issues in diverse populations.
Area of Science:
- Human adaptation to high altitude
- Genetics of hypoxia response
- Physiology of AMP-activated protein kinase (AMPK)
Background:
- Highland populations exhibit adaptations to hypoxia via the oxygen-transport cascade.
- The PRKAA1 gene, encoding AMP-activated protein kinase (AMPK), is under natural selection in Andeans and linked to fetal phenotypes.
- AMPK regulates cellular energy, ventilation, and the hypoxic ventilatory response (HVR).
Purpose of the Study:
- To identify adaptive genetic variants in highland populations related to hypoxia.
- To investigate the functional role of PRKAA1 variants in human adaptation.
- To determine the association of PRKAA1 variants with ventilatory and sleep phenotypes.
Main Methods:
- Analysis of positive selection signals in highland populations.
- Identification and genotyping of a regulatory promoter variant (rs10035235, C>T) in PRKAA1.
- Association studies with ventilatory and sleep phenotypes in Andean highlanders and lowland cohorts.
Main Results:
- A signal of positive selection was localized in the PRKAA1 gene.
- A regulatory promoter variant (rs10035235, C>T) was identified as being of adaptive significance.
- This variant is associated with ventilatory and sleep phenotypes in male Andean highlanders and sleep phenotypes in lowlanders.
Conclusions:
- A functional, adaptive, and pleiotropic regulatory variant in PRKAA1 has been identified in Andeans.
- This variant may enhance hypoxia-induced ventilation.
- The PRKAA1 variant may offer protection against sleep-disordered breathing in both high- and lowland populations.
