Highland groups have adapted to the extreme selective pressures of hypoxia at high altitude via alterations in the oxygen-transport cascade. , which encodes the catalytic subunit of the AMP-activated protein kinase (AMPK), is a notable target of natural selection in Andeans and has been associated with protective fetal phenotypes in this population. AMPK is a universal cellular energy sensor involved in a multitude of physiological processes, including ventilation and the hypoxic ventilatory response (HVR) in animal models. We localized a signal of positive selection and identified a regulatory promoter variant (rs10035235, C>T) of adaptive significance that is associated with ventilatory and sleep phenotypes in male Andean highlanders as well as sleep phenotypes in publicly available lowland cohorts. This work identifies a functional, adaptive, and likely pleiotropic regulatory variant in in Andeans that may accentuate hypoxia-induced ventilation and provide protection from sleep-disordered breathing in both high- and lowland populations.