A panel of ancestry informative markers for the complex five-way admixed South African coloured population

Abstract

Admixture is a well known confounder in genetic association studies. If genome-wide data is not available, as would be the case for candidate gene studies, ancestry informative markers (AIMs) are required in order to adjust for admixture. The predominant population group in the Western Cape, South Africa, is the admixed group known as the South African Coloured (SAC). A small set of AIMs that is optimized to distinguish between the five source populations of this population (African San, African non-San, European, South Asian, and East Asian) will enable researchers to cost-effectively reduce false-positive findings resulting from ignoring admixture in genetic association studies of the population. Using genome-wide data to find SNPs with large allele frequency differences between the source populations of the SAC, as quantified by Rosenberg et. al's In-statistic, we developed a panel of AIMs by experimenting with various selection strategies. Subsets of different sizes were evaluated by measuring the correlation between ancestry proportions estimated by each AIM subset with ancestry proportions estimated using genome-wide data. We show that a panel of 96 AIMs can be used to assess ancestry proportions and to adjust for the confounding effect of the complex five-way admixture that occurred in the South African Coloured population.

Figure 1. Admixture proportion correlation versus number of AIMs in set.

Correlation between admixture proportions estimated using AIMs and proportions estimated using genome-wide data, using AIM sets of increasing size (increments of 25) for the Cape Town study group (n = 733). A proportion of the SNPs in each set of AIMs were selected using the multiple -statistic, indicated in each panel as a percentage, while the remaining SNPs were selected using the pairwise -statistic, as described in the Methods section.

Figure 2. Barplots of ancestry proportions estimated using genome-wide data and using AIMs.

In the first panel ancestry proportions were estimated using genome-wide data. The admixed study group (sac) is ordered by proportions of African San, African non-San, European, South Asian and East Asian ancestry. In the second panel ancestry proportions were estimated using 96 AIMs. Individuals appear in the same order as in the first panel.

Figure 3. Boxplots of ancestry proportions of the Cape Town study group.

Boxplots of ancestry proportions estimated using genome-wide data and proportions estimated using the panel of 96 AIMs are shown in this figure per source population, for the Cape Town study group (n = 733).