People who are used to low-altitude environment experience several health complications, sometimes even fatal ones. Low levels of oxygen at high-altitude environment also decrease reproductive rates. One common disease seen in people that live in high-altitude environment is Monge's disease. Monge's disease is characterized by overproduction of red blood cells. Interestingly, Tibetan highland population is resistant to Monge's disease because of the decreased level of hemoglobin concentration.

EGLN1 and PPARA are correlated with hemoglobin concentration. EGLN1 encodes PHD2, prolyl hydroxylase domain-containing protein 2, which is a negative regulator of HIF-1α. PPARA encodes for PPARα, peroxisome proliferator activated receptor alpha. PPARα is regulated by HIF protein, and is essential for fatty acid metabolism. Since PPARA induces fat metabolism, it is unfavorable in hypoxic conditions because fatty acid metabolism needs more oxygen for energy production compared to glycolysis. PPARA is therefore negatively correlated with the concentration of HIF-1α. The positive selection seen in EGLN1 and PPARA, which are negatively correlated with the concentration of hemoglobin, indicates that Tibetans have a unique adaptation.

The Tibetan plateau is distinct for its extremely high elevation. Compared to other high-altitude populations, Tibetans are better adapted to the high elevations. Advantageous mutations and positive selection have resulted in genes that can adapt to high-altitude environments in Tibetan highlands. Tibetans have unique characteristics such as elevated resting ventilation and low hemoglobin count. In addition, since the Tibetan population has bee living in the area for approximately 1,110 generations, beneficial mutations have had enough time to become fixed. Tibetan population has also shown a positive selection in genes such as EGLN1, PHD2 and PPARA, all which are negative regulators of HIF-1α.