Year of Award
2024
Document Type
Dissertation
Degree Type
Doctor of Philosophy (PhD)
Degree Name
Pharmaceutical Sciences and Drug Design
Department or School/College
Department of Biomedical and Pharmaceutical Sciences
Committee Chair
Erica L. Woodahl
Commitee Members
Philippe J. Diaz, Alison E. Fohner, Travis S. Hughes, Keith K. Parker, Travis J. Wheeler
Abstract
Precision medicine aims to optimize healthcare based on individual genetic, environmental, and lifestyle factors, offering the potential to reduce health disparities. However, rural and Tribal communities remain underrepresented in precision medicine research, which threatens to exacerbate existing health inequities. My dissertation research aims to reduce health disparities in rural and Tribal communities in Montana through community-based participatory research (CBPR) and genetic studies. We partnered with research participants of the Confederated Salish and Kootenai Tribes (CSKT) on the Flathead Reservation and Shodair Children’s Hospital (Shodair) to conduct two primary studies.
In the first study, we investigated genetic and seasonal determinants of vitamin D levels among CSKT participants. We used a candidate gene approach to analyze 14 genes involved in vitamin D homeostasis among n=469 CSKT participants. We identified 5 novel genetic variants which significantly influence circulating levels of the biomarker of vitamin D3 [25(OH)D3] levels. We also observed seasonal variations in vitamin D levels, with prevalent vitamin D insufficiency during non-summer months, underscoring the need for targeted interventions.
In the second study, we conducted a genome-wide association study (GWAS) of response to antipsychotic drug, risperidone, in pediatric patients at Shodair, which serves rural areas across Montana. In our study, we genotyped n=161 patients and analyzed genomic and demographic/clinical factors influencing risperidone response. We identified nine novel genetic variants which significantly influenced risperidone response. Our findings contribute to understanding the genetic basis of risperidone response in rural pediatric populations, paving the way for personalized psychiatric care.
Our findings in both studies demonstrate inclusion of underserved rural and Tribal populations in precision medicine studies can lead to novel discoveries of genetic and non-genetic factors which influence health outcomes. Importantly, we utilized CBPR methods in both studies, which fostered trust and collaboration with the CSKT and Shodair communities. Our CBPR approach also ensured the research addressed community-specific health concerns, enhancing the impact of our findings. My dissertation advocates for increased inclusion of underserved rural and Tribal communities in precision medicine to improve health equity. Furthermore, our findings support the development of personalized interventions aimed at reducing health disparities in underserved communities.
Recommended Citation
Staples, Jack William, "GENETIC AND ENVIRONMENTAL FACTORS SHAPING PRECISION MEDICINE WITH RURAL AND TRIBAL POPULATIONS IN MONTANA" (2024). Graduate Student Theses, Dissertations, & Professional Papers. 12383.
https://scholarworks.umt.edu/etd/12383
© Copyright 2024 Jack William Staples