Dataset Information

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.

SUBMITTER: Daya M

PROVIDER: S-EPMC3869660 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Daya Michelle M van der Merwe Lize L Galal Ushma U Möller Marlo M Salie Muneeb M Chimusa Emile R ER Galanter Joshua M JM van Helden Paul D PD Henn Brenna M BM Gignoux Chris R CR Hoal Eileen E

PloS one 20131220 12

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 ...[more]

PMID: 24376522

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Project description:Introduction: Human populations are often highly structured due to differences in genetic ancestry among groups, posing difficulties in associating genes with diseases. Ancestry-informative markers (AIMs) aid in the detection of population stratification and provide an alternative approach to map population-specific alleles to disease. Here, we identify and characterize a novel set of African AIMs that separate populations of African ancestry from other global populations including those of European ancestry. Methods: Using data from the 1000 Genomes Project, highly informative SNP markers from five African subpopulations were selected based on estimates of informativeness (In) and compared against the European population to generate a final set of 46,737 African ancestry-informative markers (AIMs). The AIMs identified were validated using an independent set and functionally annotated using tools like SIFT, PolyPhen. They were also investigated for representation of commonly used SNP arrays. Results: This set of African AIMs effectively separates populations of African ancestry from other global populations and further identifies substructure between populations of African ancestry. When a subset of these AIMs was studied in an independent dataset, they differentiated people who self-identify as African American or Black from those who identify their ancestry as primarily European. Most of the AIMs were found to be in their intergenic and intronic regions with only 0.6% in the coding regions of the genome. Most of the commonly used SNP array investigated contained less than 10% of the AIMs. Discussion: While several functional annotations of both coding and non-coding African AIMs are supported by the literature and linked these high-frequency African alleles to diseases in African populations, more effort is needed to map genes to diseases in these genetically diverse subpopulations. The relative dearth of these African AIMs on current genotyping platforms (the array with the highest fraction, llumina's Omni 5, harbors less than a quarter of AIMs), further demonstrates a greater need to better represent historically understudied populations.

Project description:BackgroundGenetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification.Methodology/principal findingsHere we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (F(st)), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race.Conclusion/significanceCoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions.

Dataset Information

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

Publications

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

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