Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase (MTHFR) and EPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the MTHFR locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans. Significance The origin of Tibetans and the mechanism of how they adapted to the high-altitude environment remain mostly unknown. We conduct the largest genome-wide study in Tibetans to date. We detect signatures of natural selection at nine gene loci, two of which are strongly associated with blood phenotypes in present day Tibetans. We further show the genetic relatedness of Tibetans with other ethnic groups in China and estimate the divergence time between Tibetans and Han. These findings provide important knowledge to understand the genetic ancestry of Tibetans and the genetic basis of high-altitude adaptation.

Purpose.: To estimate the prevalence and associations of primary open angle glaucoma (POAG) in a rural population of northern China. Methods.: In a rural county in Handan, China, 6716 adults residing in 13 villages were randomly selected and participated in the study. All participants completed a comprehensive eye examination, including intraocular pressure (IOP), slit-lamp examination, and fundus evaluation. Visual fields were obtained with on glaucoma suspects. Results.: Sixty-five persons (1.2%) had POAG, with an adjusted prevalence of 1.0% (95% confidence interval [CI], 0.7% −1.3%) in those aged 40 years and older. Sex was not significantly associated with POAG (P > 0.05). Age (odds ratio [OR], 1.9; 95% CI, 1.4–2.5, for each 10-year increase), IOP (OR, 1.5; 95% CI 1.2–2.0 for each 5-mm Hg increase), axial length (OR, 1.3; 95% CI, 1.1–1.6), and moderate myopia (3.1–6.0 D; OR, 4.7; 95% CI, 1.6–13.5) increased the risk for POAG in multivariate analysis. The mean IOP of persons with POAG was 16.3 ± 3.5 mm Hg, and 90% of them presented with an IOP ≤21 mm Hg. Of those with POAG, 4.5% were blind from glaucoma in at least one eye. Conclusions.: Approximately 1% of adults aged 40 years and older living in rural China have POAG. As seen in other populations, increasing age, higher IOP, greater axial length, and having myopia were associated with POAG. Given the rapid aging and myopic shift (acquired myopia) in China's population, POAG is likely to increase in prevalence in the coming decades.