Research summary

China has the biggest population of any country in the world, accounting for about 20% of the global population. More than 95% belong to the Han ethnic group, but there are also 55 minorities, providing a rich human resource for evolutionary and population genetic studies. One of our research interests is to preserve the genetic resource of these Chinese populations and study their genetic diversity, as well as investigating the association of genetic variants with common diseases.

Research fields

1. A Genetic Resource Repository of Chinese Populations

In 1994, the Chinese Human Genome Project (CHGP) was officially initiated by the National Natural Science Foundation with one of the national key projects: Studies of gene structure in Chinese genomes. The project had two phases: 1994-1997 and 1998-2003. As part of the project, we set up and improved the method for producing cell lines, and established 733 transformed lymphoblastoid cell lines from northern and southern Han as well as 16 minority ethnic groups from the southwest and northeast of China. Together with our collaborators, the Institute of Medical Biology, the Chinese Academy of Medical Sciences, the Institute of Genetics and Development Biology, and the Chinese Academy of Science, the project collected DNA samples and established cell lines for 58 populations from 42 ethnic groups by the end of 2003. The work has thus successfully preserved the resources from these populations and provided many opportunities for subsequent studies of population genetics, genetic diversity and the evolutionary history of Chinese populations. The project has also contributed 150 cell lines (10 cell lines from each of 5 populations from our department) from this collection to the CEPH-HGDP panel (, a worldwide population sample panel widely used by international scientists for human genetic studies. We were awarded the second prize in the National Natural Science Awards in 2005 for this work (

2. Genetic Diversity and Natural Selection

Y-chromosomal polymorphisms have been widely used for studies of population genetics and human history. We identified male genetic imprints (two special Y chromosome lineages) linked to the Mongol and Manchu dynasties using Y chromosome variation (combinations of Y-SNPs and Y-STRs). We also discovered that northern and southern Chinese populations had undergone different demographic changes, which we linked to food availability during the last 50 thousand years.

Natural selection in different environments has played a role in shaping human genetic patterns. One of the consequences of this can be to produce variants that are highly differentiated between populations. We have followed up the most highly differentiated non-synonymous (amino acid-changing) SNPs identified by the HapMap project ( using resequencing data and additional tests for natural selection, and demonstrated that highly differentiated SNPs are often good indicators for positive selection in the human genome.

We have investigated the frequency distribution of disease alleles found by candidate genome studies and GWAS (Genome Wide Association Studies) of autoimmune diseases, AIDS and cancers to understand the general genetic structure of disease alleles in Chinese populations. This will also help us to further understand the demographic history of China.

3. Replicating Common Disease Association Studies

Taking advantage of the success of GWAS studies worldwide and the rich genetic resources of China, we have collected matched case and control samples for several diseases that have been of long-standing interest to the Department. These include autoimmune diseases, cancers, T2D, schizophrenia and HIV infection. We carried out replication studies on these samples and demonstrated both shared and different genetic susceptibilities for these diseases in China compared with other countries. These samples also form a good resource for further GWAS in the future and we welcome international collaborations.

Publications (*corresponding author)

1.        Jia X, Zhang F, Bai J, Gao L, Zhang X, Sun H, Sun D, Guan R, Sun W, Xu L, Yue Z, Yu Y, Fu S*. (2013)Combinational analysis of linkage and exome sequencing identifies the causative mutation in a Chinese family with congenital cataract.BMC Med Genet. 14:107. PMID:  24103489

2.        Zhang X, Qiao H, Zhao Y, Wang X, Sun H, Liu A, Xu L, Sun D, Jin Y, Yu Y, Meng X, Bai J, Chen F, Fu S*. (2012) Association of single nucleotide polymorphisms in TCF2 with type 2 diabetes susceptibility in a Han Chinese population. PLoS One. 7(12): e52938. PMID: 3534126

3.        Zhou J, Sun D, Xu L, Sun L, Fu S, Li Y*. (2011) ADAM33 as a psoriasis susceptibility gene in the Han population of northeastern China. Dermatology. 223(4):356-62. PMID: 22269827

4.        Qiao H, Zhang X, Zhao X, Zhao Y, Xu L, Sun H, Fu S*. (2012) Genetic variants of TCF7L2 are associated with type 2 diabetes in a northeastern Chinese population. Gene. 495(2):115-9. PMID: 22245614

5.        Han D, Shen C, Meng X, Bai J, Chen F, Yu Y, Jin Y, Fu S*. (2012) Methionine synthase reductase A66G polymorphism contributes to tumor susceptibility: evidence from 35 case-control studies. Mol Biol Rep. 39(2):805-16. PMID: 21547363

6.        Sun H, Bai J, Chen F, Jin Y, Yu Y, Fu S*. (2011) Lack of an association between AURKA T91A polymorphisms and breast cancer: a meta-analysis involving 32,141 subjects. Breast Cancer Res Treat. 125(1):175-9. PMID: 20464476

7.        Sun H, Bai J, Chen F, Jin Y, Yu Y, Jin L, Fu S*. (2011) RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects. Breast Cancer Res Treat. 125(1):157-61. PMID: 20454923

8.        Shen C, Sun H, Sun D, Xu L, Zhang X, Liu A, Jia X, Bai J, Chen F, Yu Y, Jin Y, Yu J, Fu S*. (2011) Polymorphisms of tumor necrosis factor-alpha and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 126(3):763-70. PMID: 20882404

9.        Sun H, Qiao Y, Zhang X, Xu L, Jia X, Sun D, Shen C, Liu A, Zhao Y, Jin Y, Yu Y, Bai J, Fu S*. (2010) XRCC3 Thr241Met polymorphism with lung caner and bladder cancer: A meta-analysis. Cancer Sci. 101(8):1777-82. PMID: 20500515

10.    Xu L, Yuan W, Sun H, Zhang X, Jia X, Shen C, Zhao Y, Sun D, Yu Y, Jin Y, Fu S*. (2011) The polymorphisms of the TNF- gene in multiple sclerosis?-a meta-analysis. Mol Biol Rep. 38(6):4137-44. PMID: 21136171

11.    Wu J, Ren X, Zhang X, Li C, Li Y, Ma H, Zhou Y, Jin Y, Chen F, Bai J, Fu S*. (2010) The vascular endothelial growth factor +405 G/C polymorphism in psoriasis. J Dermatol Sci. 57(1):62-3. PMID: 19931423

12.    Xu L, Qiao Y, Zhang X, Sun H, Wang J, Sun D, Jia X, Shen C, Zhao Y, Jin Y, Yu Y, Ling H, Wang K, Fu S*. (2011) A haplotype in the CCR5 gene promoter was associated with the susceptibility to HIV-1 infection in a northern Chinese population. Mol Biol Rep. 38(1):327-32. PMID: 20364409

13.    Xu Z, Sun H, Yu Y, Jin Y, Meng X, Sun D, Bai J, Chen F, Fu S*. (2010) Diversity of five novel Y-STR loci and their application in studies of north Chinese populations. J Genet. 89(1):29-36. PMID: 20505244

14.    Jiang J, Zhang X, Sun D, Jin Y, Bai J, Chen F, Fu S*. (2010) Study on VNTR polymorphism of gene IL-1RA in 19 Chinese populations. Int J Immunogenet. 37(2):73-7. PMID: 20002810

15.    Xu L, Qiao Y, Zhang X, Sun H, Wang J, Sun D, Jin Y, Yu Y, Chen F, Bai J, Ling H, Wang K, Fu S*. (2010) CCR2-64I allele is associated with the progression of AIDS in a Han Chinese population. Mol Biol Rep. 37(1):311-6. PMID: 19669591

16.    Xu L, Sun H, Zhang X, Wang J, Sun D, Chen F, Bai J, Fu S*. (2010) The -22018A allele matches the lactase persistence phenotype in northern Chinese populations. Scand J Gastroenterol. 45(2):168-74. PMID: 19947896

17.    Xue Y, Zhang X, Huang N, Daly A, Gillson CJ, Macarthur DG, Yngvadottir B, Nica AC, Woodwark C, Chen Y, Conrad DF, Ayub Q, Mehdi SQ, Li P, Tyler-Smith C*. (2009) Population differentiation as an indicator of recent positive selection in humans: an empirical evaluation. Genetics. 183(3):1065-77. PMID: 19737746

18.    Zheng L, Sun H, Wang J, Li S, Bai J, Jin Y, Yu Y, Chen F, Jin L, Fu S*. (2009) Y Chromosomal STR Polymorphism in Northern Chinese Populations. Biological Research. 42(4):497-504. PMID: 20140305

19.    Wang C, Chen F, Zhang X, Jin Y, Bai J, Fu S*. (2009) Polymorphic study of XRCC1 G28152A and XRCC1 C26304T in 10 Chinese populations. Biochem Genet. 47(1-2):27-32. PMID: 19067157

20.    Wu J, Chen F, Zhang X, Li Y, Ma H, Zhou Y, Jin Y, Wang H, Bai J, Zhang G, Fu S*. (2009) Association of MIF promoter polymorphisms with psoriasis in a Han population in northeastern China. J Dermatol Sci. 53(3):212-5. PMID: 19157791

21.    Wu J, Fu S, Ren X, Jin Y, Huang X, Zhang X, Bai J, Fu S*. (2009) Association of MIF promoter polymorphisms with childhood asthma in a northeastern Chinese population. Tissue Antigens. 73(4):302-6. PMID: 19317738

22.    Mao R, Fan Y, Chen F, Sun D, Bai J, Fu S*. (2008) Methylenetetrahydrofolate reductase gene polymorphisms in 13 Chinese ethnic populations. Cell Biochem Funct. 26(3):352-8. PMID: 18098118

23.    Mao R, Fan Y, Chen F, Fu S*. (2008) Genetic polymorphism of MTHFR G1793A in Chinese populations. Eur J Epidemiol. 23(5):363-8. PMID: 18409008

24.    Xue Y,  Sun D,  Daly A,  Yang F,  Zhou X,  Zhao M,  Huang N,  Zerjal T,  Lee C,  Carter NP,  Hurles ME,  Tyler-Smith C*. (2008) Adaptive evolution of UGT2B17 copy-number variation. Am J Hum Genet.  83(3):337-46. PMID: 18760392

25.    Zhang Z, Chen F, Zhang X, Jin Y, Bai J, Fu S*. (2008) PTPN22 allele polymorphisms in 15 Chinese populations. Int J Immunogenet. 35(6):433-7. PMID: 19046301

26.    Sun H, Qiao Y, Chen F, Xu L, Bai J, Fu S*. (2007) The lactase gene -13910T allele can not predict the lactase-persistence phenotype in north China. Asia Pac J Clin Nutr. 16(4):598-601. PMID: 18042517

27.    Zhang Y, Xue Y, Huang X, Ma L, Yu Y, Huang C, Zhang G, Li P, Fu S*. (2007) Genetic diversity of Y-chromosome microsatellites in the Fujian Han and the Sichuan Han populations of China. Anthropol Anz. 65(1):1-14. PMID: 17444187

28.    Xue Y, Zerjal T, Bao W, Zhu S, Shu Q, Xu J, Du R, Fu S, Li P, Hurles ME, Yang H, Tyler-Smith C*. (2006) Male Demography in East Asia: A North-South Contrast in Human Population Expansion Times. Genetics. 172(4):2431-9. PMID: 16489223

29.    Zhang X, Zhang C, Yu Y, Chen F, Li P, Fu S*. (2006) CCR2 allele polymorphisms in 15 Chinese ethnic populations. Int J Immunogenet. 33(1):45-8. PMID: 16426243

30.    Xue Y, Zerjal T, Bao W, Zhu S, Lim SK, Shu Q, Xu J, Du R, Fu S, Li P, Yang H, Tyler-Smith C*. (2005) Recent spread of a Y-chromosomal lineage in Northern China and Mongolia. Am J Hum Genet. 77(6):1112-6. PMID: 16380921

31.    Meng X, Xue Y, Sun D, Li P, Fu S*. (2005) Study on the Distribution of the MSY2 Polymorphism in 9 Chinese Populations. Anthropol Anz. 63(1):23-7. PMID: 15830585

32.    Ma L, Xue Y, Liu Y, Wang Z, Cui X, Li P, Fu S*. (2005) Polymorphism study of seven SNPs at ADH genes in 15 Chinese populations. Hereditas. 142(2005):103-11. PMID: 16970620

33.    Huang X,  Xue Y,  Liu Y,  Liu P,  Zhang C,  Li P,  Fu S*. (2004) The distribution of six biallelic polymorphisms on non-recombining segments of the Y-chromosome in five Chinese populations. Anthropol Anz. 62(4):435-44. PMID: 15648852