Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project

Abstract Imbalance of genetic resources in global population restricts the understanding of complex traits across populations. Here, we initiated the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (NGS) individuals and 5,841 high-density genotyping individuals. We identified 81.5 million SNPs and INDELs, of which 38.5% are novel. We found that 5.05% of the rare variants in WBBC were common in European population, and some trait-associated common variants in European had much lower allele frequency in Chinese. We provided a population-specific reference panel and an online imputation server (https://wbbc.westlake.edu.cn/) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we found novel selection signatures in SNX29, DNAH1 and WDR1 genes, and the selection of the alcohol metabolism genes (ADH1A and ADH1B) strengthened from about 4,000 years ago in East Asia. Genetic evidence supported the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separated the Han Chinese into subgroups, and we revealed that North Han was more homogeneous than South Han, and the history of effective population size of Lingnan began to deviate from the other three regions from 6,000 years ago. Significant selection of genes on epidermal cell differentiation was only observed in southern Chinese. Genetic divergence from north to south was more noticeable in the ancient than modern populations.