Regional Admixture Mapping and Structured Association Testing: Conceptual Unification and an Extensible General Linear Model
Year: 2006
Type: article
Abstract: Individual genetic admixture estimates, determined both across the genome and at specific genomic regions, have been proposed for use in identifying specific genomic regions harboring loci influencing phenotypes in regional admixture mapping (RAM). Estimates of individual ancestry can be used in structured association tests (SAT) to reduce confounding induced by various forms of population substructure. Although presented as two distinct approaches, we provide a conceptual framework in which both RAM and SAT are special cases of a more general linear model. We clarify which variables are sufficient to condition upon in order to prevent spurious associations and also provide a simple closed form "semiparametric" method of evaluating the reliability of individual admixture estimates. An estimate of the reliability of individual admixture estimates is required to make an inherent errors-in-variables problem tractable. Casting RAM and SAT methods as a general linear model offers enormous flexibility enabling application to a rich set of phenotypes, populations, covariates, and situations, including interaction terms and multilocus models. This approach should allow far wider use of RAM and SAT, often using standard software, in addressing admixture as either a confounder of association studies or a tool for finding loci influencing complex phenotypes in species as diverse as plants, humans, and nonhuman animals.
Source: PLoS Genetics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: Admixture Mapping for Insulin Complex Outcomes, G1474999166, G1497518678, G2137000402, G2208033956, CLINICAL NMR STUDIES AT 41T--A RESEARCH RESOURCE, G2482760120, Training Program in Rheumatic Diseases Research, UAB Statistical Genetics Post-Doctoral Training Program, G4414776803, Center for Nutrient-Gene Interaction in Cancer Prevention, Exercise Intensity, Metabolic Rate & Insulin Sensitivity, General Clinical Research Center, G5496650064, G5501604117, G6228401022, G6297008147, Program Project in the Genetics of SLE, Capitalizing upon Genetic Heterogeneity, Rheumatic Diseases Core Centers (P30), Positional Gene Identification of Complex Traits, G8345767259, G8404489359, Long-term follow-up of postobese black and white women, UAB Nutrition Obesity Research Center (NORC)
OpenAlex ID: W2095375981