Dissertation
DNA methylation signature: as a potential biomarker for addiction and psychiatric disorders
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2023
DOI: 10.25820/etd.007067
Abstract
Genome-wide association studies (GWAS) aim to understand the genetic component of complex (multifactorial) disease phenotypes, such as addiction and psychiatric disorders, which do not obey the standard Mendelian rules of inheritance. However, the heritability of addiction and psychiatric disorders cannot be explained only by the genetic variants identified by GWAS studies. Both genetic variants and environmental factors play a role in developing complex diseases. The interaction between genetic variants and the environment is translated as epigenetic modifications, which lead to changes to gene function without changes to the underlying DNA sequence itself. One of the most well-studied epigenetic modifications in humans is DNA methylation. It is established and maintained by a specialized group of enzymes called DNA methyltransferases that attach a methyl group to a cytosine nucleotide when it is usually located before guanine (CpG site). DNA methylation changes the phenotypic consequences of the genetic variants. Thus, to fully understand the functional role of potential genetic variants that are associated with addiction and psychiatric disorders it is essential to study the relationship between these genetic variants and DNA methylation of the adjacent CpG sites. Therefore, we conducted three projects to study DNA methylation and its relation to genetic variations in cocaine addiction, schizophrenia, bipolar disorder, and suicidal behavior.
My Ph.D. research contributed significantly to our understanding of the complex interaction between genetic variants and the environment by investigating how individuals' epigenetic changes (particularly changes in DNA methylation) are linked to complex disorders, with the goal of developing DNA methylation-based biomarkers. My research discovered specific DNA methylation differences linked to mental health disorders (bipolar disorder, schizophrenia, and suicidal behavior), which helps us understand the biological mechanisms underlying these diseases.
Details
- Title: Subtitle
- DNA methylation signature: as a potential biomarker for addiction and psychiatric disorders
- Creators
- Aysheh Alrfooh
- Contributors
- Marie Gaine (Advisor)Ethan Anderson (Committee Member)Ryan Smith (Committee Member)Aislinn Williams (Committee Member)Azeez Butali (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacy (Clinical Pharmaceutical Sciences)
- Date degree season
- Spring 2023
- DOI
- 10.25820/etd.007067
- Publisher
- University of Iowa
- Number of pages
- xx, 273 pages
- Copyright
- Copyright 2023 Aysheh Alrfooh
- Language
- English
- Date submitted
- 04/24/2023
- Date approved
- 05/12/2023
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 183-248).
- Public Abstract (ETD)
- Addiction and psychiatric disorders are complex conditions that are the leading cause of disability worldwide. Individuals who have a relative with these disorders are more likely to have these conditions. This suggests that these diseases are heritable, implying that they have a genetic component. As genetic factors influence the risk of developing these disorders, environmental factors influence the development of psychiatric disorders and addiction. For example, cannabis abuse during adolescence increases the lifetime risk of developing schizophrenia. The interaction of genetic and environmental factors can be translated at the molecular level through specific changes that occur above DNA without changing the sequence of the genetic material. These modifications are known as epigenetic changes. One of the most well-studied epigenetic modifications is DNA methylation. DNA methylation is the chemical addition of a methyl group (CH-3) to the DNA that can turn on or off gene function. My thesis aims to study DNA methylation and its relation to genetic variants in cocaine addiction and psychiatric disorders including schizophrenia, bipolar disorder, and suicidal behavior. Through this work, we identified specific DNA methylation differences linked to mental health disorders (cocaine addiction, bipolar disorder, schizophrenia, and suicidal behavior), which helps us understand the biological mechanisms underlying these diseases.
- Academic Unit
- Pharmacy; Craniofacial Anomalies Research Center
- Record Identifier
- 9984425199102771
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