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PMID: 15601533 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Measuring and using admixture to study the genetics of complex diseases.

Human genomics ·Vol. 1 ·No. 1 ·2003-11-00 ·Pages 52-62

Halder I, Shriver MD

Abstract

Admixture is an important evolutionary force that can and should be used in efforts to apply genomic data and technology to the study of complex disease genetics. Admixture linkage disequilibrium (ALD) is created by the process of admixture and, in recently admixed populations, extends for substantial distances (of the order of 10 to 20 cM). The amount of ALD generated depends on the level of admixture, ancestry information content of markers and the admixture dynamics of the population, and thus influences admixture mapping (AM). The authors discuss different models of admixture and how these can have an impact on the success of AM studies. Selection of markers is important, since markers informative for parental population ancestry are required and these are uncommon. Rarely does the process of admixture result in a population that is uniform for individual admixture levels, but instead there is substantial population stratification. This stratification can be understood as variation in individual admixtures and can be both a source of statistical power for ancestry--phenotype correlation studies as well as a confounder in causing false-positives in gene association studies. Methods to detect and control for stratification in case/control and AM studies are reviewed, along with recent studies showing individual ancestry--phenotype correlations. Using skin pigmentation as a model phenotype, implications of AM in complex disease gene mapping studies are discussed. Finally, the article discusses some limitations of this approach that should be considered when designing an effective AM study.

MeSH Terms
African Americans Alleles Asians Blacks Case-Control Studies Chromosome Mapping Ethnicity/genetics Forecasting Genetic Diseases, Inborn Genetic Markers Genetic Variation Genetics, Population Hispanic or Latino Humans Indians, North American Linkage Disequilibrium Models, Genetic Population Dynamics Skin Pigmentation/genetics United States Whites
Chemicals
Genetic Markers
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Halder Indrani
Department of Anthropology, Pennsylvania State University, University Park, PA 16801, USA.
Shriver Mark D
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Article Info
Journal
Human genomics
Abbr.
Hum Genomics
ISSN
1473-9542
DOI
10.1186/1479-7364-1-1-52
Published
2003-11-00
Pages
52-62
Language
English
Region
England
NLM ID
101202210
PMCID
PMC3525000
Subset
IM
Grants
NIDDK NIH HHS · DK53958 · United States
NHGRI NIH HHS · HG02154 · United States
External Links
PubMed source DOI: 10.1186/1479-7364-1-1-52 PMC Full Text View journal details
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