Abstract P102: Epigenome-wide Association Study of Measures of Fasting Glucose, Fasting Insulin, and Hba1c in Non-diabetic Individuals of European, African, and Hispanic Ancestry in the Charge Consortium
Background: Fasting glucose, fasting insulin, and hemoglobin A1c are important glycemic biomarkers and elevated levels of these markers predict future glycemic dysfunction and type-2 diabetes. Several studies have identified DNA methylation sites associated with quantitative glycemic traits and T2D. However, these studies have generally been limited in size. In this project, we aim to identify blood cells methylation signatures associated with three quantitative glycemic traits - fasting glucose (FG), log-transformed fasting insulin (logFI) and hemoglobinA1c (HbA1c) through meta-analysis of DNA methylation data from participating CHARGE Epigenetics Working Group cohorts.
Methods: We conducted a epigenome-wide meta-analysis of DNA methylation assessed with Illumina BeadChip 450K array on blood-based DNA samples, including 12,681 for FG, 11,224 for logFI, and 6358 for HbA1c, from non-diabetic participants of European, African, and Hispanic ancestry in 10 cohorts from the CHARGE Epigenetics Working Group. Mixed linear regression analyses were performed adjusting for age, sex, smoking status, cell composition, and and technical covariates, with and without adjustment for BMI. A Bonferroni corrected P value of 1.1 х 10–7 was considered significant.
Results: In combined multiethnic analysis, methylation at a total of 208 cytosine guanine dinucleotides (CpGs) were significantly associated with FG, 761 CpGs with logFI, and 109 CpGs with HbA1c. Adjustment for BMI substantially reduced the number of DNA methylation loci that met epigenome-wide significance. Biologically putative genes include CPT1A and TXNIP(FG), ABCG1 and CPT1A (logFI),and ABCG1 and MAFG (HbA1C).
Conclusion: Our findings suggest that methylation of CpG sites within multiple genes are cross-sectionally associated with glycemic biomarkers. Our results also confirm findings from prior and smaller studies, meriting further evaluation of these methylation sites and genes as novel disease risk markers.
Author Disclosures: B.A. Hidalgo: None. M. Hivert: None. J. Wessel: None. W. Guan: None. R.B. Gondalia: None. E.L.I. Salfati: None. E. Montoro Carnero: None. A.Z. Moore: None. J. Brody: None. J. Kriebel: None. J. Smith: None. W. Zhao: None. S. Ligthart: None. D. Hill: None. J.S. Pankow: None. A.Y. Chu: None.
- © 2017 by American Heart Association, Inc.