A Comprehensive Map of Genetic Variation in the World’s Largest Ethnic Group—Han Chinese

Abstract

As are most non-European populations, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our data set. Individuals from this data set came from 24 out of 33 administrative divisions across China (including 19 provinces, 4 municipalities, and 1 autonomous region), thus allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identified previously unrecognized population structure along the East-West axis of China, demonstrated a general pattern of isolation-by-distance among Han Chinese, and reported unique regional signals of admixture, such as European influences among the Northwestern provinces of China. Furthermore, we identified a number of highly differentiated, putatively adaptive, loci (e.g., MTHFR, ADH7, and FADS, among others) that may be driven by immune response, climate, and diet in the Han Chinese. Finally, we have made available allele frequency estimates stratified by administrative divisions across China in the Geography of Genetic Variant browser for the broader community. By leveraging the largest currently available genetic data set for Han Chinese, we have gained insights into the history and population structure of the world's largest ethnic group.

Population Genetic Diversity and Phylogenetic Characteristics for High-Altitude Adaptive Kham Tibetan Revealed by DNATyperTM 19 Amplification System

“…Our results showed that Han Chinese populations – long believed to the decedents of Yanhuang Emperors who shared similar cultural artifacts and underwent several southward migrations as well as an admixture with southern indigenous minorities – presented a population stratification (Wen et al, 2004). Significant genetic difference between North-China Han and South-China Han was identified, which is consistent with the earlier research findings via maternal mitochondrial, paternal Y-chromosomal and autosomal genetic materials (Chen et al, 2009; Xu et al, 2009; Nothnagel et al, 2017; Chiang et al, 2018). This North-to-South cline is dependably supported by our heat map, MDS, N-J phylogenetic relationship reconstruction and PCA analyses, as well as illustrated by the low pairwise Reynolds’ genetic distance within South Han Chinese populations and Northern Han Chinese populations and larger genetic distance between them.…”

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

“…Furthermore, in the Trans-Omics for Precision Medicine (TOPMed) Program, only $10% of its 145,000 samples are Asians (Taliun et al, 2019). In Asia, most published WGS studies have small sample sizes (Bai et al, 2018;Wong et al, 2013Wong et al, , 2014, except for two recent studies of Chinese by 1.73 and 0.13 WGS, respectively (Chiang et al, 2018;Liu et al, 2018). Extremely shallow sequencing, however, has low sensitivity to detect rare variants and, thus, limited power for evolutionary inferences and other population genetics analyses (Li et al, 2011;Han et al, 2014).…”

Testing for Hardy–Weinberg equilibrium in structured populations using genotype or low‐depth next generation sequencing data

“…Next‐generation sequencing data have become more prevalent in genetic studies as the cost of whole‐genome sequencing has decreased (Chiang et al., ; Francioli et al., ; Liu et al., ; UK10K Consortium, ). This has also led to an increased number of large‐scale sequencing studies of samples with diverse ancestries (1000 Genomes Project Consortium et al., , ).…”