Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease |
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| Authors: | Keith L Keene Josyf C Mychaleckyj Shelly G Smith Peter S Perlegas Jasmin Divers Carl D Langefeld Barry I Freedman Donald W Bowden " target="_blank">Michèle M Sale |
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| Institution: | (1) Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA;(2) Center for Public Health Genomics, University of Virginia, PO Box 800717, Charlottesville, VA 22908, USA;(3) Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA;(4) Public Health Sciences, University of Virginia, Charlottesville, VA, USA;(5) Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA;(6) Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA;(7) Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA;(8) Department of Medicine, University of Virginia, Charlottesville, VA, USA |
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| Abstract: | Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact
of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes
(T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM–ESRD,
596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for
eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP
and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly
across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates
were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed
from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls,
male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases
(r
2 = 0.101; P = 0.019) and in the combined set (r
2 = 0.131; P = 3.57 × 10−5). The absolute difference between frequencies in parental populations, absolute δ, was correlated with admixture impact for
dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact
of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding
effects due to admixture.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at |
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