Approved Research
Discovery and application of polygenic architectures of mental health traits
Lay summary
Mental health diagnoses are common in the population. A decade or so of genetics research has uncovered that these diagnoses are the result of cumulative genetic and environmental factors. Furthermore, the factors associated with whether or not someone presents symptoms of a disorder or receives a diagnosis overlap with many other aspects of the human experience. One example of this observation, termed "pleiotropy", is the overlap between regions of the DNA that associate with body composition are associated with more severe symptoms of stress following traumatic experiences.
Discoveries regarding the overlapping regions of DNA associated with two traits can be used to make conclusions about the biology that may link them. For example, one might expect gene expression in the brain to associate with mental health diagnoses but might be surprised to find that this expression in the brain overlaps with heart disease or musculoskeletal outcomes. Upon closer examination of these trait relationships, scientists have uncovered evidence that (i) evolution may help explain how our DNA influences seemingly different traits, (ii) the various ways in which DNA differs from person to person can help inform the severity of their symptoms or diagnosis, and (iii) environmental variation influences how our DNA presents itself in the forms of mental health symptoms and diagnosis.
This proposal aims to investigate different types of variation in human DNA towards improving diagnostic procedures, identification of therapeutic targets, and better modeling of symptom and disorder progression across diverse populations. Our goal is supported by three lines of inquiry:
* Use genetic association methods to find regions of human DNA that contain different classes of variation. We will use genetic and statistical methods to identify that regions and types of DNA variation most meaningful for mental health disorders, their symptoms, and their overlap with related traits.
* Identify environmental factors relevant for the DNA to affect a trait. These studies include environments like stress, traumatic experiences, workplace conditions, etc.
* Create methods to combine different types of DNA variation and predict mental health symptom severity, diagnosis, and co-morbidity or co-occurrence with other traits.
In a rolling three-year project, we will investigate how our DNA and environment influence biological pathways leading to mental health disorders and contribute to their overlap with related traits. Our findings are expected to offer explanation of the overlap between mental health and other traits, including the potential to identify treatments and treatment targets for these disorders.