Analysis of East Asia Genetic Substructure Using Genome-Wide SNP Arrays

PLoS One. 2008;3(12):e3862. doi: 10.1371/journal.pone.0003862. Epub 2008 Dec 5.

Abstract

Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Far East / ethnology
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome, Human*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Principal Component Analysis

Substances

  • Genetic Markers