First 'genetic map' of Han Chinese may aid search for disease susceptibility genes Wednesday, 25 November 2009 A pair of papers in the American Journal of Human Genetics today is highlighting the genetic and genomic variation present within the Han Chinese population. It is the largest ethnic population in the world. In the first of these papers, a Genome Institute of Singapore-led team developed a genetic map of the Han Chinese population by genotyping thousands of individuals from across China. This first historical genetic variation map is providing insights into Han Chinese population structure and evolutionary history — for instance, revealing North-South population structure in China. And down the road, researchers say, the results should pave the way for genome-wide association and other studies in the population. Based on genome-wide DNA variation information in over 6,000 Han Chinese samples from 10 provinces in China, this new map provides information about the population structure and evolutionary history of this group of people that can help scientists to identify subtle differences in the genetic diversity of Asian populations. Understanding these differences may aid in the design and interpretation of studies to identify genes that confer susceptibility to such common diseases as diabetes in ethnic Chinese individuals. Understanding these differences also is crucial in exploring how genes and environment interact to cause diseases. With the genetic map, the GIS scientists were able to show that the northern inhabitants of China were genetically distinguishable from those in the south, a finding that seems very consistent with the Han Chinese's historical migration pattern. The genetic map also revealed that the genetic divergence was closely correlated with the geographic map of China. This finding suggests the persistence of local co-ancestry in the country. "The genome-wide genetic variation study is a powerful tool which may be used to infer a person's ancestral origin and to study population relationships," said Liu Jianjun, Ph.D., GIS Human Genetics Group Leader. "For example, an ethnic Chinese born and bred in Singapore can still be traced back to his or her ancestral roots in China," Dr. Liu said. "By investigating the genome-wide DNA variation, we can determine whether an anonymous person is a Chinese, what the ancestral origin of this person in China may be, and sometimes which dialect group of the Han Chinese this person may belong to.” "More importantly, our study provides information for a better design of genetic studies in the search for genes that confer susceptibility to various diseases," he added. Of particular interest to people in Singapore are the findings that while the majority of Singaporean Chinese hail from Southern China as expected, some have a more northern ancestral origin. GIS Executive Director Edison Liu, M.D., said: "Genome association studies have provided significant insights into the genes involved in common disorders such as diabetes, high cholesterol, allergies, and neurological disorders, but most of this work has been done on Caucasian populations.” "More recently, Dr. Liu Jianjun from our institute has been working with his Chinese colleagues to define the genetic causes of some of these diseases in Asian populations," the GIS Executive Director added. "This work refined those tools so that the results will not be obscured by subtle differences in the genetic diversity of Asian populations. In the process, Dr. Liu has reconstructed a genetic historical map of the Chinese people as they migrated from south to north over evolutionary time." "There are definite differences in genetic architecture between populations," noted Chia Kee Seng, M.D., Head, Department of Epidemiology & Public Health, National University of Singapore (NUS), and Director, NUS-GIS Centre for Molecular Epidemiology. "We have seen this in the Singapore Genome Variation Project, a Joint NUH-GIS effort. Understanding these differences is crucial in exploring how genes and environment interact to cause diseases," he added. The research results published in American Journal of Human Genetics is part of a larger ongoing project on the genome-wide association study of diseases among the Chinese population. The project is a collaboration between GIS and several institutions and universities in China. In Jan. 2009, Nature Genetics published the findings of researchers at the GIS and Anhui Medical University, China, on psoriasis, a common chronic skin disease. In that study, led by Dr. Liu Jianjun at the GIS and Dr. Zhang Xuejun at the Anhui Medical University, the scientists discovered a genetic variant that provides protection against the development of psoriasis. The collaboration's recent discovery of over a dozen genetic risk variants for systematic lupus erythematosus (SLE) in the Chinese population was published in Nature Genetics in Oct. 2009. In a second AJHG paper, a Chinese research team genotyped more than 1,700 Han Chinese individuals from dozens of sites in China as part of another study aimed at understanding the genetic and genomic patterns within the Han Chinese population. The researchers genotyped 1,721 Han Chinese samples at about 160,000 SNPs for this paper. They collected more than 1,500 of the samples, while 44 were collected through the Human Genome Diversity Panel project and 171 were collected in Beijing and Denver as part of the HapMap project. That team detected north-south stratification similar to that reported by the Singapore-led team, though they designated three main Han Chinese clusters from northern, southern, and central parts of China. Again, individuals from the cities — in this case Beijing, Shanghai, and Guangzhou — did not represent populations that were as homogenous as those in other locations were. The researchers also found some SNPs that were strongly differentiated in different parts of the country. For instance, they reported, the frequency of SNPs in the genes FADS2 and HCP5 varied from north to south. Based on several simulated GWAS, each involving 300 cases and 300 controls, the team suggested that even the relatively subtle genetic variation within China could lead to excess false-positive associations. "Although differences in allele frequencies among Han Chinese clusters are small, our study has demonstrated the importance of accounting for population stratification in order to reduce false-positive associations," the researchers wrote. Reference: Genetic Structure of the Han Chinese Population Revealed by Genome-wide SNP Variation Jieming Chen, Houfeng Zheng, Jin-Xin Bei, Liangdan Sun, Wei-hua Jia, Tao Li, Furen Zhang, Mark Seielstad, Yi-Xin Zeng, Xuejun Zhang, Jianjun Liu The American Journal of Human Genetics, 25 November 2009, doi:10.1016/j.ajhg.2009.10.016 Genomic Dissection of Population Substructure of Han Chinese and Its Implication in Association Studies Shuhua Xu, Xianyong Yin, Shilin Li, Wenfei Jin, Haiyi Lou, Ling Yang, Xiaohong Gong, Hongyan Wang, Yiping Shen, Xuedong Pan, Yungang He, Yajun Yang, Yi Wang, Wenqing Fu, Yu An, Jiucun Wang, Jingze Tan, Ji Qian, Xiaoli Chen, Xin Zhang, Yangfei Sun, Xuejun Zhang, Bailin Wu and Li Jin The American Journal of Human Genetics, 25 November 2009, doi:10.1016/j.ajhg.2009.10.015 ......... ZenMaster
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