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

Stephanie J. Loomis, Adrienne Tin, Josef Coresh, Eric Boerwinkle, James S. Pankow, Anna Köttgen, Elizabeth Selvin, Priya Duggal

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalGenetic epidemiology
Volume43
Issue number7
DOIs
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I), R01HL087641, R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The work of AK was funded by DFG KO 3598/3-1 and KO 3598/4-1. SL was supported by an institutional training grant from the NIH/NHLBI (T32 HL007024). This study was also supported by NIH/NIDDK grants K24DK106414 and R01DK089174 to Dr. Selvin. Reagents for the 1,5-anhydroglucitol assays were donated by GlycoMark, Inc. Reagents for the glycated albumin assays were donated by the Asahi Kasei Corporation. Reagents for the fructosamine assays were donated by Roche Diagnostics Corporation.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

  • 1,5-AG
  • fructosamine
  • glycated albumin
  • glycemic biomarkers
  • heritability

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