In the Han Chinese Genomes Database (PGG.Han), we designedly select and include only individuals of Han Chinese ancestry, particularly for the purpose of imputation and GWAS in the Han Chinese population. All the participants are 18 years of age or older who contributed DNA to the project. The ancestry of participants is determined based on self-reported data and their genetic profile. In the current release of the PGG.Han database, we collect data of 114,783 individuals in total, including whole-genome sequencing data of 12,197 samples and genome-wide single nucleotide polymorphism (SNP) data of 102,586 samples. With these more than 100K Han Chinese samples being whole-genome sequenced to high coverage (~30 – 80×), or low-coverage (~1.7 – 4×), or high-density genome-wide SNP genotyped or imputed, we constructed the first and the largest reference panel specific to the Han Chinese population, a.k.a., Han100K. See the description below and the Table 1 for more detailed information.
Totally around 20,000 Han Chinese individuals with whole genomes sequenced using next-generation sequencing are archived in PGG.Han, including three deep-sequencing data sets (~30 – 80×) (n=300), and two low-pass sequencing data sets (~1.7×, n=11,670; and ~4×, n=180). The deep-sequencing data sets include 300 Han Chinese samples with whole genomes deep-sequenced (~30 – 80×), of which 131 samples from 30 administrative divisions representing 28 dialects across China were collected and sequenced to high coverage (~30 – 60×) by Population Genomics Group (PGG); 90 samples (overlapping with CHB and CHS in the 1000 Genomes Projects) were sequenced by BGI-Shenzhen at a high depth (~80×) (Lan et al., 2017); another 98 samples were also sequenced to high coverage (~30×) and obtained from a previous study (Sung et al., 2012).
Whole genome low-pass sequencing data
The genomes of 11,670 women Han Chinese were sequenced by the CONVERGE project as a control group for the investigation of major depressive disorders (Chiang et al., 2017). Although in a much lower coverage (~1.7×), this data set provides a catalog of 25,057,223 variants for the Han Chinese population and is also included in the PGG.Han.
Genome-wide SNP data
The high-density genome-wide SNP genotyped data of 102,586 samples are contributed by the collaborators of PGG.Han (see About for the list of collaborators), which were collected from previous GWAS projects, only non-patient (control) are retained. Using all the whole-genome sequencing data of Han Chinese samples as reference data, the 102,586 samples are carefully imputed so that the final data set 8,056,973 genome-wide SNPs.
The fine-scale genetic structure of the Han Chinese population
The 100K Han Chinese individuals formed a distinct cluster from the surrounding groups including minority groups in China and other neighboring countries, suggesting a full-identity of Han Chinese people in terms of overall genetic make-up. On the other hand, genetic differentiation within the Han Chinese population is discerned and 6 sub-groups are identified, i.e., Northwest Han (NWH), Northeast Han (NEH), Central China Han (CCH), Southwest Han (SWH), Southeast Han (SEH), and South coast Han (SCH). Overall, the main difference is between northern and southern subgroups, consistent with previous observations (Chen et al., 2009; Qin et al., 2014; Xu et al., 2009), while southern subgroups show higher divergence than northern subgroups. We further screened nested AIMs panels for detecting population structure and controlling population stratification in association studies. We provided high-quality individual-level variant data for future genotype imputation, population genetics analysis and association studies. The reference panel provided here is expected to greatly facilitate current and future GWAS or candidate-gene based association studies in Han Chinese and related Asian populations.
Table 1. Summary of the data sets included in PGG.Han
|Data Source||Data Type||Sample Size||Sequencing Coverage||Geographical Coverage||Language Coverage||References|
|The Han Chinese Genomes Project||Genotyping||102586||NA||34 divisions||28 dialects||PGG.Han|
|The Han Chinese Genomes Project||WGS||131||~30 – 60×||30 divisions||28 dialects||PGG.Han|
|CONVERGE||WGS||11670||~1.7×||24 divisions||NA||(Chiang et al., 2018)|
|The 1000 Genomes Project||WGS||208||~4×||NA||NA||(The-1000-Genomes-Consortium et al., 2015)|
|HCC samples||WGS||98||~30×||Southern China||NA||(Sung et al., 2012)|
|BGI-Shenzhen||WGS||90||~80×||NA||NA||(Lan et al., 2017)|
WGS: Whole Genome Sequencing; NA: Not available.
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- Chiang, C.W.K., Mangul, S., Robles, C., and Sankararaman, S. (2018). A Comprehensive Map of Genetic Variation in the World's Largest Ethnic Group-Han Chinese. Mol Biol Evol 35, 2736-2750.
- Chiang, C.W.K., Mangul, S., Robles, C.R., Kretzschmar, W.W., Cai, N., Kendler, K.S., Sankararam, S., and Flint, J. (2017). A comprehensive map of genetic variation in the world's largest ethnic group - Han Chinese. Carbohydrate Polymers 75, 104-109.
- Lan, T., Lin, H., Zhu, W., Laurent, T., Yang, M., Liu, X., Wang, J., Wang, J., Yang, H., Xu, X., et al. (2017). Deep whole-genome sequencing of 90 Han Chinese genomes. Gigascience 6, 1-7.
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- Sung, W.K., Zheng, H., Li, S., Chen, R., Liu, X., Li, Y., Lee, N.P., Lee, W.H., Ariyaratne, P.N., Tennakoon, C., et al. (2012). Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet 44, 765-769.
- The-1000-Genomes-Consortium, Auton, A., Brooks, L.D., Durbin, R.M., Garrison, E.P., Kang, H.M., Korbel, J.O., Marchini, J.L., McCarthy, S., McVean, G.A., et al. (2015). A global reference for human genetic variation. Nature 526, 68-74.
- Xu, S., Yin, X., Li, S., Jin, W., Lou, H., Yang, L., Gong, X., Wang, H., Shen, Y., Pan, X., et al. (2009). Genomic dissection of population substructure of Han Chinese and its implication in association studies. Am J Hum Genet 85, 762-774.