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. 2013 Jul 1;4(1):13.
doi: 10.1186/2041-2223-4-13.

Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel

Caroline M Nievergelt  1 , Adam X Maihofer, Tatyana Shekhtman, Ondrej Libiger, Xudong Wang, Kenneth K Kidd, Judith R Kidd
Affiliations

Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel

Caroline M Nievergelt et al. Investig Genet. .

Abstract

Background: Accurate determination of genetic ancestry is of high interest for many areas such as biomedical research, personal genomics and forensics. It remains an important topic in genetic association studies, as it has been shown that population stratification, if not appropriately considered, can lead to false-positive and -negative results. While large association studies typically extract ancestry information from available genome-wide SNP genotypes, many important clinical data sets on rare phenotypes and historical collections assembled before the GWAS area are in need of a feasible method (i.e., ease of genotyping, small number of markers) to infer the geographic origin and potential admixture of the study subjects. Here we report on the development, application and limitations of a small, multiplexable ancestry informative marker (AIM) panel of SNPs (or AISNP) developed specifically for this purpose.

Results: Based on worldwide populations from the HGDP, a 41-AIM AISNP panel for multiplex application with the ABI SNPlex and a subset with 31 AIMs for the Sequenome iPLEX system were selected and found to be highly informative for inferring ancestry among the seven continental regions Africa, the Middle East, Europe, Central/South Asia, East Asia, the Americas and Oceania. The panel was found to be least informative for Eurasian populations, and additional AIMs for a higher resolution are suggested. A large reference set including over 4,000 subjects collected from 120 global populations was assembled to facilitate accurate ancestry determination. We show practical applications of this AIM panel, discuss its limitations for admixed individuals and suggest ways to incorporate ancestry information into genetic association studies.

Conclusion: We demonstrated the utility of a small AISNP panel specifically developed to discern global ancestry. We believe that it will find wide application because of its feasibility and potential for a wide range of applications.

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Figures

Figure 1
Figure 1
Inferred population structure of the HGDP subjects based on the 41-AIM panel with clusters ranging from K2 - K7.
Figure 2
Figure 2
Principal component analysis (PCA) based on genotype data of 41 AIMs including 4,018 subjects from 120 populations from the HGDP, HapMap and Yale collections. Individual values of subjects belonging to the same population are averaged to highlight the relative location of specific populations.
Figure 3
Figure 3
Eigenvalues of the first 15 principal components (PCs) indicating that most genetic variation among the seven continental regions captured by the 41-AIM panel is accounted for by the first 5 PCs.
Figure 4
Figure 4
PC plots of 4,018 reference subjects based on genotype data from the 41-AIM panel. Subjects are color coded according the geographic sample origin. Admixed populations, African Americans and Mexicans are indicated by open symbols (see text). The % of variation explained ranges from 27.6% for PC1 to 6.2% for PC3.
Figure 5
Figure 5
PC plots of the first five PCs for a visual inspection of a large population sample collected in Southern California (black). Subjects from 107 typical reference populations are color coded. The % of variation explained is indicated in parentheses for each PC.
Figure 6
Figure 6
Comparison of individual admixture estimates based on a large GWAS-derived marker panel and the 41-AIM panel in admixed populations collected in Southern California. Self-identified Hispanic-White and Native American subjects show a wide range in the degree of Native American and European ancestry proportions (panels A and C). Self-identified African Americans show a range in the degree of African and European ancestry proportions (panels B and D).
See this image and copyright information in PMC

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