Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children

Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Human genomics (Impact Factor: 2.15). 01/2011; 5(2):79-89. DOI: 10.1186/1479-7364-5-2-79
Source: PubMed


Type 2 diabetes represents an increasing health burden. Its prevalence is rising among younger age groups and differs among racial/ethnic groups. Little is known about its genetic basis, including whether there is a genetic basis for racial/ethnic disparities. We examined a multi-ethnic sample of 253 healthy children to evaluate associations between insulin-related phenotypes and 142 ancestry-informative markers (AIMs), while adjusting for sex, age, Tanner stage, genetic admixture, total body fat, height and socio-economic status. We also evaluated the effect of measurement errors in the estimation of the individual ancestry proportions on the regression results. We found that European genetic admixture is positively associated with insulin sensitivity (S I ), and negatively associated with the acute insulin response to glucose, fasting insulin levels and the homeostasis model assessment of insulin resistance. Our analysis revealed associations between individual AIMs on chromosomes 2, 8 and 15 and these phenotypes. Most notably, marker rs3287 at chromosome 2p21 was found to be associated with S I ( p = 5.8 × 10(-5)). This marker may be in admixture linkage disequilibrium with nearby loci ( THADA and BCL11A ) that previously have been reported to be associated with diabetes and diabetes-related phenotypes in several genome-wide association and linkage studies. Our results provide further evidence that variation in the 2p21 region containing THADA and BCL11A is associated with type 2 diabetes. Importantly, we have implicated this region in the early development of diabetes-related phenotypes, and in the genetic aetiology of population differences in these phenotypes.

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Available from: Krista Casazza, Aug 14, 2014
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    • "as previously described (Casazza et al. 2009). A panel of 142 AIMs (Klimentidis et al. 2011) was used to estimate the genetic admixture proportions of each subject. The information provided by these markers reveals each subject's estimated admixture percentage for geographically separated West African, Amerindian, and European parental populations by using the maximum likelihood algorithm described by (Parra et al. 1998). "
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    • "During a meta-analysis of three genome-wide association studies with individuals of European descent Zeggini et al. found evidence for an association of a SNP (rs7578597) in exon 24 of THADA and the susceptibility for T2D [5]. Further indication for a correlation between THADA and T2D was presented in several other publications [11,14,16,17,19], one reported an altered expression of THADA in pancreatic islets, using data from the Diabetes Genome Anatomy Project (DGAP) database [11]. In other investigations no correlation was detected [6-8,10,12,13,15,18,20], except for one publication [9], which reported an association between THADA SNP rs7578597 and a 2-h insulin level during an oral glucose tolerance test but no significant association between the THADA SNP and T2D risk, rendering the association disputable. "
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