Quantitative genetic analysis of arterial oxygen saturation in Tibetan highlanders

This study was designed to test the hypothesis that genetic differences inferred from biological kinship relationships among individuals contribute to individual variation in percentage of oxygen saturation of arterial hemoglobin (SaO2) in a high-altitude native population. SaO2 data were obtained by pulse oximetry from 354 nonpregnant, healthy Tibetan residents of Pen-Dri, two rural agropastoral villages at 3800-4065 m altitude in Lhasa Municipal District, Tibet Autonomous Region, China. Statistical analyses of these data from 46 pedigrees tested the hypothesis of a significant genetic contribution to SaO2 variation. The average SaO2 was 89.4 +/- 0.2%, with a range of 76-97%. Additive genetic effects account for 44% of the interindividual phenotypic variation in SaO2 in the sample. Complex segregation analysis and variance decomposition analysis determined that 21% of the total phenotypic variation could be explained by a major gene influencing SaO2. Homozygotes for the low-SaO2 allele have a mean SaO2 of 83.6%, whereas heterozygotes and homozygotes for the high-SaO2 allele have means of 87.6% and 88.3%, respectively. This confirms findings in another Tibetan sample and extends the known geographic distribution of the major gene. These results suggest the hypothesis that individuals with the dominant allele for higher SaO2 have a selective advantage in their high-altitude hypoxic environment.