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dc.contributor.authorGrimsby, Jonna L
dc.contributor.authorPorneala, Bianca C
dc.contributor.authorYang, Quanhe
dc.contributor.authorDupuis, Josée
dc.contributor.authorLiu, Tiebin
dc.contributor.authorYesupriya, Ajay
dc.contributor.authorChang, Man-Huei
dc.contributor.authorNed, Renee M
dc.contributor.authorDowling, Nicole F
dc.contributor.authorKhoury, Muin J
dc.contributor.authorVassy, Jason Lyell
dc.contributor.authorFlorez, Jose Carlos
dc.contributor.authorMeigs, James Benjamin
dc.date.accessioned2013-03-29T20:19:11Z
dc.date.issued2012
dc.identifier.citationGrimsby, Jonna L., Bianca C. Porneala, Jason L. Vassy, Quanhe Yang, José C. Florez, Josée Dupuis, Tiebin Liu, et al. 2012. 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). BMC Medical Genetics 13:30.en_US
dc.identifier.issn1471-2350en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10482581
dc.description.abstractBackground: 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.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2350-13-30en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433372/pdf/en_US
dash.licenseLAA
dc.titleRace-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)en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Medical Geneticsen_US
dash.depositing.authorVassy, Jason Lyell
dc.date.available2013-03-29T20:19:11Z
dc.identifier.doi10.1186/1471-2350-13-30*
dash.authorsorderedfalse
dash.contributor.affiliatedFlorez, Jose
dash.contributor.affiliatedMeigs, James
dash.contributor.affiliatedVassy, Jason


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