Impact of Tibetan Ancestry on Respiratory Control and Central Sleep Apnea in Hypoxia

The onset of altitude-induced central sleep apnea (CSA) varies among individuals and may be influenced by genetic factors affecting respiratory control. Tibetans, who have undergone high-altitude adaptation over generations, may exhibit physiologic traits that protect against CSA. This study investigated the impact of Tibetan ancestry on respiratory control and hypoxia-induced CSA. Nine healthy unacclimatized Tibetans living in Switzerland for at least 5 years and 20 Caucasians (all males; median[IQR] age: 28 [27-32] vs. 24 [23.5-26] years; median[IQR] BMI: 23.8 [23.1-28] vs. 22.1[21.2-23.1]kg/m²) underwent two full polysomnographies, one at low altitude and one in a hypoxic chamber simulating 3500 m. The apnea-hypopnea index (AHI) and the percentage of sleep spent in periodic breathing (PB) were calculated. A hyperoxic hypercapnic ventilatory response (HCVR) test and hypoxic ventilatory response tests at rest (HVRr) and during exercise (HVRe) were performed. Parameters were compared between groups using non-parametric tests. At simulated altitude, Tibetans exhibited a significantly lower AHI (51.2 [12.7-72.1]/h vs. 107.0 [36.7-140.3]/h; p = 0.0231) and spent less sleep time in PB (27.6 [2.6-44.5]% vs. 58.8 [14.0-89.0]%; p = 0.0334) compared to Caucasians. HCVR did not differ significantly between groups (Tibetans: 1.983 [1.349-2.224] L/min/mmHg; Caucasians: 2.227 [1.698-3.071] L/min/mmHg; p = 0.2167). Tibetans showed a significantly lower HVRr (Tibetans: 0.001 [-0.211-0.074] L/min/%/kg; Caucasians: 0.384 [0.160-0.637] L/min/%/kg; p = 0.0112) and a blunted HVRe (Tibetans: 0.311 [0.225-0.789] L/min/%/kg; Caucasians: 0.806 [0.518-1.196] L/min/%/kg; p = 0.0448). These results indicate that Tibetan ancestry is associated with a partial protection from hypoxia-induced central sleep apnea, likely related to a blunted hypoxic ventilatory response. These findings suggest that inherited differences in ventilatory control may modulate breathing stability during sleep at high altitude.