Pilot work of the 10K Chinese People Genomic Diversity Project along the Silk Road suggests a complex east-west admixture landscape and biological adaptations.

Genomic sources from China are underrepresented in the population-specific reference database. We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups (1,081 Sinitic, 56 Mongolic, 40 Turkic, and 30 Tibeto-Burman people) living in North China included in the 10K Chinese People Genomic Diversity Project (10K_CPGDP) to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China. We observed a population split between Northwest Chinese minorities (NWCMs) and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs. The observed population substructures among ethnically/linguistically diverse NWCMs suggested that differentiated admixture events contributed to the differences in their genomic and phenotypic diversity. We estimated that the Dongxiang, Tibetan, and Yugur people inherited more than 10% of the Western Eurasian ancestry, which is much greater than that of the Salar and Tu people (<7%), while Han neighbors showed less West Eurasian ancestry (∼1%-3%). Male-biased admixture introduced Western Eurasian ancestry in the Dongxiang, Tibetan, and Yugur populations. We found that the eastern-western admixture in NWCMs occurred ∼800-1,100 years ago, coinciding with intensive economic and cultural exchanges during the Tang and Song dynasties. Additionally, we identified the signatures of natural selection associated with cardiovascular system diseases or lipid metabolism and developmental/neurogenetic disorders. Moreover, the EPAS1 gene showed relatively high population branch statistic values in NWCMs. The well-fitted demographical models presented the vast landscape of complex admixture processes of the Silk Road people, and the newly reported functionally important variations suggested the importance of including ethnolinguistically diverse populations in Chinese genetic studies for uncovering the genetic basis of complex traits/diseases.