Life Sciences Commons^™

Examining Genetically-Informed Etiologic Models Of Co-Occurring Posttraumatic Stress Disorder And Recreational Cannabis Use Among College Students, Terrell A. Hicks

Theses and Dissertations

The college years encompass a period of increased risk recreational cannabis use (RCU), as well as a time of increased risk for trauma exposure and developing posttraumatic stress disorder (PTSD). Given the high co-occurrence between RCU and PTSD, and the potentially negative consequences of the two (e.g., worse academic outcomes), there is a need to understand the etiologic mechanisms of these commonly co-occurring conditions. Two primary phenotypic models exist: self-medication model (i.e., PTSD to RCU) and the high-risk model (i.e., RCU to PTSD). To date, there are two existing studies longitudinally examining the etiologic models proposed to explain co-occurring RCU …

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …

Identifying Genes Downstream Of Mef2 That Influence Ethanol Sedation In Drosophila Melanogaster, Ananya Talikoti

Theses and Dissertations

Alcohol use disorder is a global public health issue that affects millions across the world. It can result in negative physical and mental health outcomes, and currently treatment options are limited and rates of relapse are high. Identifying genes that affect aspects of ethanol behaviors in model organisms, such as Drosophila melanogaster, can serve to eventually develop more robust therapeutic interventions for those experiencing alcohol dependence. Previous studies have identified a relationship between a person's initial sensitivity to alcohol and their abuse potential for the drug in later life. Therefore, we can study sedation behaviors in Drosophila melanogaster to …

Mef2-Bound Genes May Influence Ethanol Sedation In Drosophila Melanogaster, Katlyn M. Myers

Theses and Dissertations

Alcohol Use Disorder (AUD) is a global health issue that affects millions of people every year. This disorder has serious negative mental and physical consequences. Currently, treatment options for this disorder are largely limited to psychological therapy, with very few medications available to treat it. Being able to identify the environmental and genetic components that influence AUD can help improve diagnosis and treatment options. Previous studies in humans have shown a link between initial sensitivity and risk for alcohol abuse. Our laboratory uses Drosophila melanogaster as a model to study the genetic and environmental components of alcohol-related behaviors. Previous lab …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Natural And Anthropogenic Drivers Of Tree Evolutionary Dynamics, Brandon M. Lind

Theses and Dissertations

Species of trees inhabit diverse and heterogeneous environments, and often play important ecological roles in such communities. As a result of their vast ecological breadth, trees have become adapted to various environmental pressures. In this dissertation I examine various environmental factors that drive evolutionary dynamics in threePinusspecies in California and Nevada, USA. In chapter two, I assess the role of management influence of thinning, fire, and their interaction on fine-scale gene flow within fire-suppressed populations of Pinus lambertiana, a historically dominant and ecologically important member of mixed-conifer forests of the Sierra Nevada, California. Here, I find evidence …

Investigation On Genetic Modifiers Of Age At Onset Of Major Depressive Disorder, Huseyin Gedik

Theses and Dissertations

Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Pnpase In C. Elegans: Mutagenic Analysis To Complement Knockdown Studies, Danielle K. Seibert

Theses and Dissertations

PNPase is a gene implicated as a potential target for cancer therapy; human mutations also present with deafness, myopathies, and neuropathies. In this study, C. elegans was used to investigate the effect of knocking out PNPase in a whole animal. C. elegans knockdown studies have reported an extended lifespan via an increase in ROS production. Further noted are larger mitochondria and an increase in fzo-1 expression. Knockout animals previously constructed using CRISPR/Cas9 were used for this study. We aimed to confirm these findings validating previous studies. It was discovered that PNPase knockout animals demonstrated a similar lifespan extension that was …