Whole-genome sequencing pilot of the Central Asian Genomic Diversity Project reveals distinct histories, adaptation, and introgression

Central Asians are underrepresented in genomic research, limiting insights into their history and medical risk. We established the Central Asian Genomic Diversity Project and sequenced whole genomes of 166 individuals from 20 Central Asian and Afghanistan Hazara groups. Analyses reveal marked differentiation driven by varying West/East Eurasian ancestry; Tajiks align with West Eurasians, Dungans with East Asians. We identify four geographically structured Turkic-related clusters, two Indo-European clines, and long-range migration events, including Siberian links in Hazaras and Sino-Tibetan ties in Dungans. Admixture dates cluster ~650-1,000 years ago, coinciding with the Song-Yuan era and Mongol expansion. Variant discovery reveals distinct distributions of medically relevant variants and group-specific selection signals in metabolic, immune, and neurological pathways. Subsistence practice shifts correlate with trait-associated variation. Neanderthal-like and Denisovan-like segments show group-specific associations with immunity, psychiatric risk, drug metabolism, and type 2 diabetes. These data clarify Central Asian evolutionary history and inform precision medicine.