This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

ORCID

http://orcid.org/0000-0002-0937-5525

Date of Award

Spring 5-15-2020

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Human & Statistical Genetics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Substance use disorders are a serious threat to public health with devastating social, economic, and health impacts on affected individuals and their families. This dissertation aims to improve understanding of substance use disorders in three parts: first, an epidemiological project examining smoking cessation and e-cigarette use at a population level; second, a genetic project examining the role of genetic variants on tobacco, alcohol, cannabis, and cocaine use; and finally, a review of the utility of polygenic risk scores in predicting risk of substance use behaviors. Cigarette smoking is a leading cause of preventable death, accounting for over 480,000 deaths in the United States annually. Smoking is linked to heart disease, lung disease, and multiple cancers, and on average smokers die 10 years earlier than nonsmokers. In Chapter 2 I demonstrate the trends in smoking prevalence and smoking behaviors since 2006 in two U. S. national surveys while accounting for demographic shifts in the population that influence smoking behaviors. In addition, I demonstrate the association of electronic cigarettes with past 12 month quit attempts and successful smoking cessation at the population level. Numerous genome-wide association studies provide strong evidence for the genetic contribution to substance use disorders. Specifically, multiple studies have shown association between variants in the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster on chromosome 15 and nicotine use disorder in European ancestry populations. In Chapter 3 I demonstrate that this association is specific to nicotine use disorder and was not associated with alcohol, cannabis, and cocaine use disorders in our study population. Substance use disorders are genetically complex, and there may be common underlying environmental and genetic risk factors that predispose to substance use behaviors. With the publication of large meta-analyses of genome-wide association studies, polygenic risk scores can now be used to measure genetic liability. Chapter 4 explores the utility of polygenic risk scores for exploring the genetic etiology of disease and the genetic correlations between them. Overall, this dissertation advances our understanding of substance use disorders by incorporating population based evidence, genetic risk factors, and polygenic risk.

Language

English (en)

Chair and Committee

Laura Bierut

Committee Members

Arpana Agrawal, Christina Gurnett, John Rice, Nancy Saccone,

Available for download on Wednesday, May 15, 2120

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