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

Yann C Klimentidis, Jasmin Divers, Krista Casazza, T. Mark Beasley, David B. Allison, Jose R. Fernandez

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (S1), 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 S1 (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.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalHuman Genomics
Volume5
Issue number2
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 2
Insulin
Phenotype
Type 2 Diabetes Mellitus
Insulin Resistance
Body Height
Genome-Wide Association Study
Linkage Disequilibrium
Population Genetics
Ethnic Groups
Adipose Tissue
Fasting
Homeostasis
Age Groups
Chromosomes
Economics
Glucose
Health

Keywords

  • Ancestry-informative marker
  • Genetic admixture
  • Genetic association
  • Insulin sensitivity
  • Type 2 diabetes

ASJC Scopus subject areas

  • Drug Discovery
  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children. / Klimentidis, Yann C; Divers, Jasmin; Casazza, Krista; Beasley, T. Mark; Allison, David B.; Fernandez, Jose R.

In: Human Genomics, Vol. 5, No. 2, 2011, p. 79-89.

Research output: Contribution to journalArticle

Klimentidis, Yann C ; Divers, Jasmin ; Casazza, Krista ; Beasley, T. Mark ; Allison, David B. ; Fernandez, Jose R. / Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children. In: Human Genomics. 2011 ; Vol. 5, No. 2. pp. 79-89.
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