Published in:
Open Access
01-11-2014 | Short Communication
Variants associated with type 2 diabetes identified by the transethnic meta-analysis study: assessment in American Indians and evidence for a new signal in LPP
Authors:
Anup K. Nair, Yunhua Li Muller, Nellie A. McLean, Maryam Abdussamad, Paolo Piaggi, Sayuko Kobes, E. Jennifer Weil, Jeffrey M. Curtis, Robert G. Nelson, William C. Knowler, Robert L. Hanson, Leslie J. Baier
Published in:
Diabetologia
|
Issue 11/2014
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Abstract
Aim/hypothesis
A recent genome-wide trans-ancestry meta-analysis identified seven new loci associated with type 2 diabetes. We assessed the replication of the seven lead single nucleotide polymorphisms (SNPs) and evaluated these loci for additional signals in American Indians.
Methods
Seven SNPs were genotyped in 7,710 individuals from a longitudinally studied American Indian population, and associations with type 2 diabetes, BMI and related phenotypes were assessed. Previous genome-wide association study (GWAS) data from these individuals were used to screen for additional type 2 diabetes signals at these loci. A variant independent of the trans-ancestry meta-analysis was identified within LPP, and its replication was assessed in an additional 3,106 urban American Indians.
Results
SNP rs6813195 near to TMEM154 was nominally associated with type 2 diabetes (p = 0.01, OR 1.12 [95% CI 1.03, 1.22]) and adiposity: the type 2 diabetes risk allele was associated with a lower percentage body fat (β = −1.451%, p = 4.8 × 10−4). Another SNP, rs3130501 near to POU5F1–TCF19, was associated with BMI (β = −0.012, p = 0.004), type 2 diabetes adjusted for BMI (p = 0.02, OR 1.11 [95% CI 1.02, 1.22]), 2 h glucose concentrations (β = 0.080 mmol/l, p = 0.02) and insulin resistance estimated by homeostatic model (β = 0.039, p = 0.009). The independent variant identified at the LPP locus in our American Indian GWAS for type 2 diabetes was replicated in the additional samples (all American Indian meta-analysis, p = 8.9 × 10−6, OR 1.29 [95% CI 1.15, 1.45]).
Conclusions/interpretation
For two of the seven newly identified variants, there was nominal evidence for association with type 2 diabetes and related traits in American Indians. Identification of an independent variant at the LPP locus suggests the existence of more than one type 2 diabetes signal at this locus.