Exploration of the Impact of Smoking on Atherosclerosis through DNA Methylation Pubblico

Abstract

Atherosclerosis is a cardiovascular disease (CVD) which is the leading cause of death in the United States. Cigarette smoking is a known risk factor for CVD and many other chronic diseases. Led by development of micro-array, we obtained genome-wide DNA methylation data of 67 pairs of monozygotic twins to investigate the relationship between cigarette smoking, DNA methylation and atherosclerosis. We assessed the association between smoking and intima-media thickness, a quantitative measurement of subclinical atherosclerosis. Comparing to smoking-related DNA methylation sites from publications, we successfully replicated 17 DNA methylation sites. 16 of these sites are significantly associated with IMT adjusting age, body mass index and six cell traits (granulocyte, monocyte, natural killer cells (NK), B cell, CD4+ and CD8+ T cells) at alpha level of 0.05. After performing linear mixed effect model which conditioned on smoking status and adjusted for chip effect and co-twin effect, we found two significant loci: cg03991871 in AHRR (Beta-coefficient = -0.0503, p-value = 0.0267) and cg06126421 in 6p21.33 (Beta-coefficient= -0.0604, p-value = 0.0088). The result of our study suggested that DNA methylation might mediate the effect of cigarette smoking on atherosclerosis, and the smoking-related DNA methylation markers could potentially improve the prediction of atherosclerosis and CVD.

Table of Contents

BACKGROUND. 1

METHODS. 4

Data source. 4

DNA methylation methods. 5

Phenotypic Measurements. 6

Statistical Analysis. 6

RESULTS. 8

DISCUSSION. 9

Strength. 11

Limitation. 12

FUTURE DIRECTION. 13

REFERENCES. 15

TABLES. 18

FIGURES. 21

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MSPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Parola chiave	DNA Methylation Atheroslcerosis Cigarette Smoking
Committee Chair / Thesis Advisor	Sun, Yan, Emory University

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