Wednesday, July 30, 2008

Diabetes and African admixture

several interesting things in this paper:
- comparison of three admixture estimation methods and using various number of markers
- looking at the effect of admixture on association between diabetes and variants in diabetes candidate genes.

Probably the most important finding is the high proportion of African ancestry in females with diabetes, compared to female controls, male cases and controls.
Their interpretation:
If AA females with T2DM have genes of “African descent” that are involved in energy storage and expenditure, but also influence or are influenced by gender-specific pathways, when exposed to a westernized lifestyle, these individuals will be at an increased risk of obesity and subsequently developing T2DM.
also, their finding makes sense in terms of:
the unexplained increase in risk for having a family history of ESRD that is present among African American women, relative to men (Freedman et al. 2005; McClellan et al. 2007)
Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease.
Keene KL, Mychaleckyj JC, Leak TS, Smith SG, Perlegas PS, Divers J, Langefeld CD, Freedman BI, Bowden DW, Sale MM.
Hum Genetics Online First 2008 Jul 25.
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 x 10(-5)). The absolute difference between frequencies in parental populations, absolute delta, 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.

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