Heritability analysis of nontraditional glycemic biomarkers in the Atherosclerosis Risk in Communities Study

Genet Epidemiol. 2019 Oct;43(7):776-785. doi: 10.1002/gepi.22243. Epub 2019 Jun 19.

Abstract

Nontraditional glycemic biomarkers, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are potential alternatives or complement to traditional measures of hyperglycemia. Genetic variants are associated with these biomarkers, but the heritability, or extent to which genetics control their variation, is not known. We estimated pedigree-based, SNP-based, and bivariate heritabilities for traditional glycemic biomarkers (fasting glucose, HbA1c), and nontraditional biomarkers (fructosamine, glycated albumin, 1,5-AG) among white participants in the Atherosclerosis Risk in Communities (ARIC) Study (N = 400 first-degree relatives from sibships, N = 5,575 unrelated individuals). Pedigree-based heritabilities (representing heritability from the entire genome) for nontraditional biomarkers were substantial (0.44-0.55) and comparable to HbA1c (0.34); the fasting glucose estimate was nonsignificant. SNP-based heritabilities (representing heritability from common variants) were lower than pedigree-based heritabilities for all biomarkers. Bivariate heritabilities showed shared genetics between fructosamine and glycated albumin (0.46 pedigree-based, 1.00 SNP-based) and glycated albumin and 1,5-AG (0.50 pedigree-based, 0.47 SNP-based). Genetic factors contribute to a considerable proportion of the variance of fructosamine, glycated albumin, and 1,5-AG and a portion of this heritability likely comes from common variants.

Keywords: 1,5-AG; fructosamine; glycated albumin; glycemic biomarkers; heritability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / genetics*
  • Biomarkers / metabolism*
  • Blood Glucose / metabolism
  • Female
  • Fructosamine / blood
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Humans
  • Hyperglycemia / genetics*
  • Inheritance Patterns / genetics*
  • Male
  • Middle Aged
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Serum Albumin / metabolism

Substances

  • Biomarkers
  • Blood Glucose
  • Glycation End Products, Advanced
  • Serum Albumin
  • Fructosamine
  • Glycated Serum Albumin