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New approaches to disease mapping in admixed populations

Abstract

Admixed populations such as African Americans and Hispanic Americans are often medically underserved and bear a disproportionately high burden of disease. Owing to the diversity of their genomes, these populations have both advantages and disadvantages for genetic studies of complex phenotypes. Advances in statistical methodologies that can infer genetic contributions from ancestral populations may yield new insights into the aetiology of disease and may contribute to the applicability of genomic medicine to these admixed population groups.

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Figure 1: Admixture leads to variation in genome-wide and local ancestry.

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Acknowledgements

The authors are grateful to N. Patterson, D. Reich, A. Williams and N. Zaitlen for helpful discussions. This work was funded by US National Institutes of Health grants RC1 GM091332 (B.P. and A.L.P.), R01 AR050267 and R01 DK071185 (M.F.S.).

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Correspondence to Michael F. Seldin.

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The authors declare no competing financial interests.

Related links

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FURTHER INFORMATION

Michael F. Seldin's homepage

Alkes L. Price's homepage

DATABASES

1000 Genomes Project

Human Genome Diversity Project genotypes

International HapMap Project and International HapMap 3 Project

SOFTWARE

ADMIXMAP software

ANCESTRYMAP software

EIGENSOFT software

GEDI-ADMX software

HAPAA software

HAPMIX software

LAMP and WINPOP software

MALDsoft software

MIXSCORE software

SABER software

Glossary

Admixture mapping

A technique for mapping a risk locus for a specific trait based on a statistical signal of unusual local ancestry at the risk locus.

Ancestry-informative markers

(AIMs). Markers with large differences in allele frequency between two or more populations that can be used to infer genetic ancestry.

Cline

A continuum of genetic ancestry formed by migration or admixture between two populations.

Genome-wide ancestry

The overall genetic ancestry of an individual as determined from SNP genotypes or other data distributed across autosomal chromosomes.

Hidden Markov model

(HMM). A generalization of a mixture model in which data are generated as a function of unknown (hidden) states, with transitions between states governed by a Markov process.

Imputation

The inference of genotypes of markers that have not been directly genotyped by making use of information from haplotype reference panels such as the HapMap or 1000 Genomes panels.

Local ancestry

The genetic ancestry of an individual at a particular chromosomal location, defined as 0, 1 or 2 copies from each ancestral population considered.

Multi-way admixture

We use this term to indicate admixture between more than two continental population groups, such as in Latinos who descend from admixture between Europeans, Native Americans and West Africans.

Principal components analysis

A dimensionality reduction technique used to infer continuous axes of variation in genetic data, often representing genetic ancestry.

Two-way admixture

In this article, this term indicates admixture between two continental population groups, such as in African Americans who descend from admixture between Europeans and West Africans.

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Seldin, M., Pasaniuc, B. & Price, A. New approaches to disease mapping in admixed populations. Nat Rev Genet 12, 523–528 (2011). https://doi.org/10.1038/nrg3002

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