Dissertation
Addiction, mental health, and infectious disease: a complex web of genetic interactions
Doctor of Philosophy (Ph.D.), Drexel University
01 Oct 2014
DOI:
https://doi.org/10.17918/etd-6424
Abstract
Opiate, dopamine and GABA addictions are complex diseases with strong genetic components. These three substance disorders represent significant costs to the global judicial and healthcare systems. The treatment of addiction is further confounded by the co-occurrence of other pathologies that complicate treatment regimes. For example, addiction and mental health are well-characterized co-morbidities. Mental health conditions such as depression, bipolar disorder and schizophrenia have clear genetic synergies between the prevalence of one mental health condition and addiction. This proposal focuses on the characterization of addiction hotspots in the genome, their interplay with mental health genetics and then examines how infectious disease burden is correlated to the rise of immune and addiction variants. Molecular genetics, metabolism analyses, epigenetic and association studies have contributed to current understandings of the genetic components of addiction disorder phenotypes. The resulting literature curated gene sets can be used to identify the modules and pathways mediating shared addiction, mental health and immune disorders. Studying addiction, mental health and immune genes in a geographically diverse sample of human populations is critical to understanding the role that evolutionary factors play in the rise and maintenance of variation potentially underlying addiction phenotypes. These human population comparisons are possible due to the recent expansion of human polymorphism databases, such as the HapMap Project, the Human Genome Diversity Panel and the 1000 genomes datasets. Careful comparisons of allele frequencies in human populations can point to those polymorphisms for which both functional and evolutionary histories converge to either promote or inhibit addiction, mental health, and immune susceptibility. We can project curated addiction genes onto gene ontology categories and cellular pathways to draw a bioinformatics portrayal of addiction and its interplay with mental health and immunity. These addiction genes lists as well as schizophrenia, depression, and bipolar disorder gene sets can be further projected onto the genome to portray the overlap between addiction and mental health disorders. This can also serve as a tool to discover additional genes that play a candidate role in mental illness and addiction. Functionally annotating these regions using existing databases such as the Kyoto Encyclopedia of Genes and Genomes allows for robust characterization of the roles that genes and genomic regions play in modulating addiction phenotypes. This approach enables the identification of candidate genes sitting adjacent to known addiction hotspot genes and the subsequent identification of the candidate polymorphisms in a diverse array of human populations. Finally the addition of new databases of genome wide association studies can inform candidate polymorphisms for addiction, mental health and immune response to infectious disease.
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Details
- Title
- Addiction, mental health, and infectious disease
- Creators
- Latifa Fatima Jackson - DU
- Contributors
- Aydin Tözeren (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 6424; 991014632177604721