Doctor of Philosophy (PhD)
Dr. Tricia LeVan
Dr. Paraskevi Farazi
Dr. Jill Poole
Dr. Christopher Wichman
CC16, asthma, COPD, genetic risk score
INVESTIGATION OF CUMULATIVE GENETIC RISK AND CC16 IN ADULT ASTHMA AND COPD POPULATIONS
Kelli C. Gribben, Ph.D.
University of Nebraska Medical Center, 2022
Supervisors: Paraskevi A. Farazi and Tricia D. LeVan, Ph.D.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) have complex etiologies and lack biological predictors that can be used for primary prevention, early detection, progression, or monitoring. Genetic risk scores (GRS) aggregate genetic effects from GWAS-identified susceptibility variants associated with a trait. GRS may provide opportunities to improve disease prediction to inform public health and clinical interventions. Asthma GRS studies utilizing multi-ethnic populations are scarce and there is a need for GRS to be evaluated in independent study populations.
The Club Cell Secretory Protein (CC16) is a promising biomarker for asthma and COPD. Several gaps exist in the literature regarding CC16’s role in asthma and COPD. This dissertation addressed several key gaps in the literature by utilizing three different study populations: National Health and Nutrition Examination Survey (NHANES), Agricultural Lung Health Study (ALHS), and a Midwest United States Veteran population. The aims addressed the questions: 1) Is a GRS, based on external asthma GWAS, associated with asthma in an independent study population, NHANES, and does smoke exposure (i.e. cotinine) affect associations between GRS and asthma?, 2) Are CC16 polymorphisms associated with adult asthma, subtypes and asthma control in adults from ALHS?, 3) Are CC16 protein levels associated with lung function, smoking status or smoking history among a Veteran COPD population? Results of these studies will add new knowledge of the potential utility of an asthma GRS and CC16 biomarker to ultimately reduce burden and improve clinical management of asthma and COPD.
Gribben, Kelli C., "Investigation of Cumulative Genetic Risk and CC16 in Adult Asthma and COPD Populations" (2022). Theses & Dissertations. 632.
Available for download on Saturday, April 20, 2024