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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2012

Open Access 01-12-2012 | Research article

Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)

Authors: Jonna L Grimsby, Bianca C Porneala, Jason L Vassy, Quanhe Yang, José C Florez, Josée Dupuis, Tiebin Liu, Ajay Yesupriya, Man-Huei Chang, Renee M Ned, Nicole F Dowling, Muin J Khoury, James B Meigs, the MAGIC Investigators

Published in: BMC Medical Genetics | Issue 1/2012

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Abstract

Background

Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.

Methods

We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05.

Results

RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71).

Conclusion

At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.
Appendix
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Metadata
Title
Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)
Authors
Jonna L Grimsby
Bianca C Porneala
Jason L Vassy
Quanhe Yang
José C Florez
Josée Dupuis
Tiebin Liu
Ajay Yesupriya
Man-Huei Chang
Renee M Ned
Nicole F Dowling
Muin J Khoury
James B Meigs
the MAGIC Investigators
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2012
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-13-30

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