ORCID

https://orcid.org/0000-0002-6215-8466

Date of Award

12-19-2023

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

Cigarette smoking has been linked to adverse health outcomes, including several forms of cancer, respiratory and cardiovascular disease, and dementia. Despite the public health campaigns aimed at reducing tobacco use, the behavior remains prevalent, and its association with various organs is an active area of research. Recent studies showed that smoking behaviors have strong genetic contributions. Through genome-wide association studies, the genetic risk score of individuals can be created and used as a basis for more effective and precise healthcare solutions. Chapter 2 explores the creation of a polygenic risk score (PRS) for smoking cessation and its utility in two clinical trials. PRS for the later age of smoking initiation, and the combined PRS of four smoking behaviors (later age of smoking initiation, persistent smoking, cigarettes per day, and ever smoking) predicted bio-verified smoking abstinence. With this information, chapter 3 examines the utility of PRS in a more general setting (UK Biobank) with healthy individuals. The PRS for persistent smoking significantly predicted smoking cessation in the UK Biobank population. Also, individuals were divided into 7 groups of different PRS for persistent smoking, and those with the risk score of bottom 10% and top 10% had 3 years difference in median age of smoking cessation. Chapter 4 extends the relationship between genetics and smoking behavior to an actual association with the relatively understudied organ in tobacco research: the brain. It is widely known that smoking adversely affects the lungs and heart, but studies on the relationship between smoking and the brain are comparatively lacking. Using the smoking questionnaire data, brain imaging data, and genetic data from the UK Biobank, I found that the genetic risk for smoking is not associated with brain volume, while ever smoking was significantly negatively associated with the total brain volume. Furthermore, I also identified several regions more significantly associated with a history of daily smoking than the other regions. Chapter 5 explores the association of smoking with the structural and functional connectivity of the brain. The UK Biobank provides diffusion MRI-derived phenotypes that measure structural connectivity within and across the regions of the brain. I examined the inter/intra-regional tracts that are more affected by smoking than others. For the functional connectivity, I used the resting-functional MRI-derived phenotypes and found that the functional connectivity within frontal lobe regions was modestly associated with ever smoking. Overall, this dissertation advances our understanding of the clinical utility of PRS for smoking behaviors, and the association of smoking behavior with the brain.

Language

English (en)

Chair and Committee

Laura Bierut

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Genetics Commons

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