Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Elizabeth C. Prom-Wormley


Introduction. Tobacco use is a public health crisis with nearly 500,000 Americans suffering premature mortality attributable to tobacco use in 2014. New development efforts have created new nicotine delivery systems whose health consequences are not yet fully understood such as electronic cigarettes (ECIG). It is possible there are shared genetic and environmental factors that influence an individual’s liability to initiate cigarette (CIG) or ECIG use, as both systems are designed to deliver nicotine.

Methods. Four study designs were used to resolve the genetic and environmental influences that underlie CIG and ECIG initiation. A twin study, scoping review, genome-wide association study (GWAS), and moderation model examined these potential sources of variation.

Results. The twin study suggested there were shared genetic factors between CIG and ECIG initiation. Univariate GWAS analysis of ECIG found no genome-wide significant hits among self-identified white participants. Genome-wide polygenic scores also showed no association between CIG and ECIG initiation. Statistical evidence of a weak interaction between ECIG coupon receipt, income level, and CIG use was reported. A review of tobacco use measures in genetically informative samples found that how individual studies measured different aspects of tobacco use lead to different genome-wide significant results.

Conclusions. These analyses suggest there are shared genetic and environmental influences between CIG and ECIG. Low sample sizes may have contributed to non-significant findings of measured molecular genetic effects, though genome-wide suggestive findings indicate further research is needed. Further, aggregating genome-wide association study results by biological function may increase the consistency of findings.


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