NEW YORK (GenomeWeb News) – A pair of papers in the American Journal of Human Genetics today are highlighting the genetic and genomic variation present within the Han Chinese population.
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. The genetic variation they detected 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.
"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," senior author Liu Jianjun, leader of the GIS Human Genetics Group, said in a statement. "More importantly, our study provides information for a better design of genetic studies in the search for genes that confer susceptibility to various diseases."
More than 90 percent of individuals in China belong to the Han Chinese population. Nevertheless, most large international genetic studies have sampled Han Chinese individuals from just a few sites, revealing a fraction of the genetic diversity thought to exist in the population.
To remedy this, Jianjun and his team obtained samples from 6,580 Han Chinese individuals in ten Chinese provinces, along with 1,050 samples from the cities of Beijing and Shanghai and another 570 samples from Han Chinese individuals living in Singapore. They then genotyped the samples using the Illumina Human 610-Quad BeadChip arrays.
They found that individuals from the same provinces tended to roughly cluster together. And within a region in China's Guangdong province, the researchers found genetic differentiation that correlated with language dialect groups.
The researchers were also able to distinguish a gradient of genetic patterns that varied from north to south, though they didn't see the same differentiation when looking from east to west. In contrast to the pattern in the provinces, though, the cities (Beijing, Shanghai, and Singapore) were home to individuals with a range of north-south genetic patterns.
Their results suggest most — but not all — Han Chinese individuals in Singapore are most closely related to individuals in southern China. Meanwhile, comparisons with HapMap samples were consistent with the notion that individuals from Japan are more closely related to northern than southern Han Chinese individuals.
In the future, the team hopes the genetic map will inform the way future GWAS are designed and interpreted in China. Indeed, the team's simulations illustrate how inaccurate associations can result from GWAS that are done without a clear understanding of population structure.
"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," GIS Executive Director Edison Liu, who was not directly involved in the current research, said in a statement. "This work refined those tools so that the results will not be obscured by subtle differences in the genetic diversity of Asian populations."
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.
For that paper, researchers genotyped 1,721 Han Chinese samples at about 160,000 SNPs using Affymetrix or Illumina microarrays. 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.
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.
And 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.
"[A]lthough 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.