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)

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.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).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.