A pilot work of the 10K Chinese People Genomic Diversity Project reveals complex east-west admixture landscape and biological adaptations

The 10K_CPGDP Consortium has released one of its pilot works detailing the genetic diversity and admixture history of ethno-linguistically diverse groups residing in the Silk Road region of China. The study involved whole-genome sequencing or genome-wide genotyping data of 1,207 individuals from four linguistically diverse groups, providing insights into their genetic architecture and adaptative history. The authors observed a population differentiation between Northwest Chinese minorities (NWCMs) and Han Chinese dating back to the Upper Paleolithic period with subsequently complex interactions, with further differentiation within NWCMs during the Neolithic. The study estimates that certain genetically underrepresented human groups, such as the Dongxiang, Tibetan, and Yugur in the Silk Road region, inherited some measurable but low Western Eurasian ancestry, significantly more than other groups like the Salar and Tu. The research also identified signatures of natural selection associated with cardiovascular diseases, lipid metabolism, and developmental/neurogenetic disorders, highlighting the importance of diverse populations in genetic studies to uncover the genetic basis of complex traits and diseases.

The authors demonstrated the significant genetic influence of ancient Trans-Eurasian migration and cultural exchange on the gene pool of Silk Road populations. A high-quality dataset comprising over 16.4 million SNPs and 1.9 million InDels was generated. Genetic affinity and population structure of NWCMs were analyzed using PCA, outgroup f₃-statistics, and TreeMix, revealing genetic relationships with ancient and modern Eurasian populations. ADMIXTURE analysis identified four major ancestral components in NWCMs, with significant contributions from East Eurasian and West Eurasian sources. Sex-biased admixture patterns were observed in the Dongxiang, Tibetan, and Yugur populations, with a greater contribution from East Eurasian females and West Eurasian males compared to other NWCMs. Genetic differentiation among NWCMs and neighboring populations reflects complex demographic histories and admixture events. These findings offer valuable insights into the genetic diversity and population history of NWCMs along the Silk Road.

The team also investigates the complex interplay between demographic admixture events and local adaptation in shaping disease susceptibility and phenotypic diversity in NWCM populations. High-confidence natural selection signatures, particularly in PRIM2 and PDE4DIP, associated with cardiovascular diseases, and NBPFs 9/20/25P, linked to developmental and neurogenetic diseases, were identified across all NWCM populations. Signatures of local adaptation specific to certain NWCM populations were identified, including NOTCH2, which is linked to vascular, renal, and hepatic development in Tibetan and Yugur populations; DDAH1, associated with cardiovascular disease and pulmonary hypertension in Dongxiang, Tibetan, and Yugur populations; GALNT2, involved in triglyceride levels and type 2 diabetes in the Tibetan population; and MLIP, related to the negative regulation of cardiac muscle hypertrophy in response to stress, and observed in Salar and Tu populations. Enrichment analyses reveal that candidate genes are involved in biological processes such as angiogenesis regulation and neuron projection morphogenesis. The cold, dry winters and hot summers experienced by NWCM populations, combined with dietary habits characterized by high salt and oil consumption and a preference for meat, may have contributed to the observed selection characteristics. These findings underscore the intricate relationship between genetic admixture and local adaptation in shaping disease- and health-related traits in NWCM populations.

“We are inspired that advances in human genomic projects and revolutionary sequencing techniques have profoundly enhanced our understanding of human genetic history and its influence on the genetic determinants of diseases and traits. This pilot study sheds light on the significant impact of complex evolutionary events on human health and diseases, emphasizing the critical role of genomic technologies in improving health outcomes among underrepresented populations in genomic research. The findings underscore the contributions of the human genome project in integrating genomic tools into clinical practice, including applications in disease risk assessment, prenatal testing, and clinical decision-making. These advancements, particularly through large-scale Chinese genomic initiatives, promote health equity and advance the realization of precision medicine. This work demonstrates the transformative potential of genomic technologies in fostering equitable healthcare outcomes in the era of precision medicine.” Chao Liu – the lead author of the study – noted.

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