Epigenome-wide Association of HbA1c among the Non-diabetic Twins Open Access

Abstract

Aim: Conducted an epigenome-wide association study to identify novel HbA1c-associated CpG sites in whole blood DNA.

Patients & methods: We performed an epigenome-wide association study of hyperglycemia among 258 non-diabetic male twins using linear mixed effect models. DNA Methylation at each cytosine-phosphate-guanine (CpG) sites as a function of HbA1c, adjusting for age, smoking, BMI and calculated proportion of peripheral blood leukocytes subtypes.

Results: Regression analysis showed that identified three CpG sites significantly associated with HbA1c according to within-twin effect after multiple testing correction (FDR less than 0.05), including cg00725722 (CCDC74B, p-value = 2.74 × 10^-7), cg19142411(RAD52, p-value = 9.54× 10^-8), cg00773483 (RNF150; p-value = 2.04 × 10^-7). We also identified 25 CpG sites significantly associated (FDR<0.05) with HbA1C via between-twin effect (unshared association between co-twins).

Conclusion: This epigenome-wide study discovered significant association (FDR <0.05) between HbA1c and DNA methylation level in within-twin and between-twin effects. There were no DNA methylation sites significantly associated with HbA1C in both between-twin effect and within-twin effect after multiple testing correction, which suggested that for different HbA1C-associated DNA methylation sites, the epigenetic associations were mostly driven by either shared or unshared factors, but not both.

Table of Contents

Introduction -----------------------------1

Methods ---------------------------------3

Results -----------------------------------5

Discussion------------------------------- 6

Conclusion -------------------------------9

Reference --------------------------------11

Tables -----------------------------------14

Figures and Figure Legends -------------19

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	Epigenetic HbA1c Hyperglycemia
Committee Chair / Thesis Advisor	Yan Sun, Emory University

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