Gene-lifestyle Interactions in Coronary Artery Diseases Open Access

Abstract

Coronary artery disease (CAD) is the pre-eminent cause of death. Both genetic and lifestyle factors such as cigarette smoking and physical activity (PA) contribute to development of CAD. Over 160 loci have been linked with risk of CAD in genome-wide association studies. However, the interaction between genetic predisposition and individual lifestyle factors in CAD remains unclear. This dissertation presents research focused on exploring gene-lifestyle interactions for CAD among populations of European ancestry using data from two of the largest biobank cohorts. Multiple cardio-metabolic traits mediate the genetic effects of CAD, so this dissertation also aims to characterize the gene-lifestyle interaction driven by different mediating traits. In addition, gene-lifestyle interactions can be an important part of CAD heritability and accounting for gene-lifestyle interactions can potentially increase the power when detecting CAD-associated loci. Results of this dissertation have shown that the absolute risk elevation in CAD due to smoking is stronger among those with higher genetic susceptibility and the interaction can be driven by different mediating cardio-metabolic traits when different domains of smoking behavior is considered. Also, no evidence of interaction was identified between genetic predisposition and physical activity for CAD. Two GWASs of CAD accounting for gene-smoking interaction and gene-physical activity interaction found no novel loci, and results have shown no gain of power when a joint two degree of freedom approach was implemented. Future studies should consider exploring gene-lifestyle interactions for complex diseases such as CAD on both additive and multiplicative scale considering potential different mediating pathways. Novel methods should be developed to better incorporate gene-lifestyle interactions in genetic associations of complex diseases.

Table of Contents

Chapter 1. Introduction to gene-lifestyle interactions in coronary artery diseases

Chapter 2. Assessment of gene-smoking interaction in coronary artery diseases

Chapter 3. Assessment of gene-physical activity interaction in coronary artery diseases

Chapter 4. Genome-wide association studies of coronary artery diseases accounting for gene-smoking interaction or gene-physical activity interaction

Chapter 5. Summary and future directions

References

About this Dissertation

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School	Laney Graduate School
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	lifestyle Gene-environment interaction coronary artery disease
Committee Chair / Thesis Advisor	Yan V Sun, Emory University Viola Vaccarino, Emory University
Committee Members	Yijuan Hu, Emory University Marta Gwinn, Emory University Arshed A Quyyumi, Emory University

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