How Genome-Wide Variation within the Han Chinese Population Affects Study Design
By Brian Z. Ring, PhD, Director of Technology of YiGene Inc., and Principal Investigator of Applied Genomics
A scan of a rack of magazines these days will likely find at least one article discussing the emergence of China onto the world stage, its headline usually following the standard formula of “The (Sleeping/Red) (Dragon/Giant) (Awakes/Rises)”. Yet despite China’s growing importance to the world news, the genetics of the Han people, the dominant ethnic group in China and the largest ethnic group in the world, has been relatively poorly studied. The HAPMAP project, which characterized 45 Han individuals, not surprisingly revealed that this group has distinct variation from other ethnic groups, yet unveiled little about variation within the Han population. Other studies have been of a small scale or followed only maternal and paternal lineages through Y chromosome and mitochondrial studies. These have suggested an interesting variation within the Han population, primarily on a north-south axis, but not much more.
Fortunately two studies recently published in the American Journal of Human Genetics are shedding more light on the genome wide variation within the Han population. The studies, one led by Jin Li of Fudan University, the second by Jianjun Liu of the Genome Institute of Singapore, each independently studied thousands of autosomal snps in samples collected from several regions in China (the studies utilized 160K snps, 1700 individuals, and 350K snps, 6000 individuals, respectively). The studies by and large reveal a similar story: both show that while the Han Chinese population is comparatively uniform, significant variation exists, and the variation largely seems to correspond to the known north-south settlement of China by this ethnic group. This pattern, as measured by the Genome Institute of Singapore’s study, accounts for roughly 0.4% of the genetic variance within this population. Though small, both studies confirm that this variation could affect genome wide association studies if a geographically diverse population is used without proper stratification. This information will help better guide these surveys and help avoid false positive candidates.
Another important result from these studies is the flip side of the observed genetic variance; though of statistical significance, it is nonetheless relatively small. This is encouraging to a variety of efforts underway in China which presume a relatively flat genetic landscape. Drug development has been carried out, for the most part, in Europe and the United States, and thus the clinical populations have been comprised largely of those of European heritage. This leads to concern on the applicability of the direct translation of these results to other populations. To address this bias, as well as to entail lower costs in the increasingly cost conscious pharmaceutical market, an increasing number of clinical trials are being carried out within China. If there existed strong regional differences in the population’s genetic makeup, these studies would have to be carefully constructed to either properly stratify their cohorts or limit them to a genetically uniform region, especially in trials where there is a potentially significant genetic component to the response to the candidate compound.
While these two studies do not reveal that the intra-ethnic variation within the Han population can be ignored in such studies, it appears it’s likely of a small enough scale to not adversely affect current clinical trial strategies. Similarly, efforts to employ known associations between drug response and genetic variation in crafting public health care services are not disrupted by this new information. For example, cytochrome P450 2D6 is responsible for the metabolism of a wide variety of commonly prescribed drugs. However, mutant forms of this enzyme, though rare in the West, have been revealed by the HAPMAP project to affect roughly a third of Han Chinese. This is encouraging efforts to determine if genotyping prior to prescribing affected drugs could lead to improved health care delivery and lower costs. If there was strong variation within the Han population then strategies created with the HAPMAP data as its basis would not be applicable. Instead, these recent results will serve to improve ongoing studies and ensure meaningful results. Additional studies of genome wide variation within the Han population, encompassing more regions of China, will further fill in the picture and allow an even more refined approach to future translational studies.
Dr. Brian Ring received his PhD in Molecular Biology from Cornell University and currently lives and works in Beijing, China.
Yigene is a Beijing based personal genomics service company. Yigene is working with the Chinese CDC and other public institutions to determine the best methods and practices of translating genetic discoveries to the Chinese public health market.
Image: Wellcome Trust, L0004700, “The doctor is feeling the pulse of a woman patient. Her wrist is supported on a small red bolster. The doctor touches the pulse only with his finger-tips, without looking at the woman,” Watercolour By: Zhao Pei Qun
Comments
4 Responses to “How Genome-Wide Variation within the Han Chinese Population Affects Study Design”
Leave a Reply
-
Categories
-
Archives
-
Blogroll
-
HUGO on LinkedIn
Excellent overview of the issues. The south-to-north genetic gradient is seen throughout the Asian continent with greater diversity in the south. Moreover, the geographical and language associations of genetic groups is quite strong.
Yes, the population genetics that is now feasible is very interesting. The consistent results of both papers promises that focused analyses could reveal more complex smaller scale or overlapping migration patterns, roles of family or clan networks in population dynamics, and the relations of language and dialect groups. Hopefully these papers will also encourage expanded studies encompassing more regions and subpopulations across Asia, tying the story of the Han population’s genetic geography with that of the rest of the continent.
Dear Dr Ring,
It is heartening to find your comments.The study of genomics of Han Chinespopulation will definitely help us in understaning the migration of Han
Chineses people from prehistoric past to present.Recently my student Sri J
Nayak has identified ALDH2*2 allele (Alcohol protective gene) among the most primitive tribal populations of Orissa,suggesting possible inflow of the han chinese gene to Orissan tribal populations (austroasiatic) in
prehistoric/neolithic time.
Please communicate views
Prof P.K.Das
Dear Dr Riang,
It is heartening to find your comments.The study of genomics of Han Chinese population will definitely help us in understanding the migration of Han Chineses people from prehistoric past to present.Recently my student Sri J. Nayak has identified ALDH2*2 allele (Alcohol protective gene) among the most primitive tribal populations of Orissa,the BOND suggesting possible inflow of the Han chinese gene to Orissan tribal populations (austroasiatic) in prehistoric/neolithic time or vice-versa. A collabotive study is needed
Please communicate views
With warm regards
Prof P.K.Das