Date of Award

Spring 1-1-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Kenneth Krauter

Second Advisor

Robin Dowell

Third Advisor

Matt McQueen

Fourth Advisor

Rob Knight

Fifth Advisor

Shelley Copley

Abstract

The human oral microbiome is formed early in development. Its composition is influenced by environmental factors including diet, substance use, oral health, and overall health and disease. The influence of human genes on the composition and stability of the oral microbiome is still poorly understood. To uncover genetic effects, I studied both environmental and genetic characteristics in a large twin sample studied for the salivary microbiome as well as in a large cohort of unrelated individuals. In a subsample of the Colorado Twin Registry I identify several significantly heritable features of the salivary microbiome. I also show that heritability persists in twins even when their cohabitation changes. The heritability of these traits correlates with the cumulative genetic contributions of over half a million single nucleotide sequence variants measured in a different population of unrelated individuals. I show that two new loci on chromosomes 7 and 12 are associated with the most heritable traits. Use of a two-stage strategy provides a powerful method to refine complex phenotypes prior to genetic analyses and improves power to detect associations by eliminating the need for “P-hacking” and reducing the multiple testing error correction. In addition to investigating the association of host genetics with the salivary microbiome the environmental factor of substance use was also examined. A cohort of subjects selected for either no substance use or heavily using either marijuana, tobacco, or amphetamine were used to find community level difference with the salivary microbiome and the use of each substance. Specific taxa also had varying levels of abundance between tobacco users and non-tobacco users. Together these studies demonstrate that both host genetics and substance use are associated with differences in the salivary microbiome.

Included in

Genetics Commons

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