Psychiatric Disorder Genomic Risk Scores as a Correlate of Disease Activity and Progression in Multiple Sclerosis
Abstract
What is the problem we are trying to solve? Mental health disorders, like depression and anxiety, are associated with many poor outcomes, including lower quality of life and increased risk of death. Individuals with an autoimmune disease, such as multiple sclerosis (MS), are at higher risk for mental health disorders compared to people without an autoimmune disease. Mental health disorders are also underdiagnosed and undertreated in people with MS. These mental health disorders in MS are also linked with faster MS disability and larger cognitive impairments. The reasons for this are unknown, but it may be related to genetics. We want to improve the identification of mental health disorders and disease activity and disability in those with MS by studying genetic factors related to mental health. There are many of these genetic factors that play a role in mental health and, together, they are called "mental health genetic scores." We are requesting funds to pay for analyzing this information to answer our research questions. What are our research questions? (1) Do people with MS that have a higher mental health genetic score also have a higher chance of having a mental health disorder? (2) Do people with MS, and any of the following, (A) increased MS relapse activity, (B) faster MS progression, or (C) worse cognition, also have a higher mental health genetic score? How are we addressing the FY19 MSRP Focus Area "Correlates of Disease Activity and Progression in MS?" We want to determine whether the mental health genetic scores are connected to disease activity and progression in MS. We will use existing Canadian samples and then confirm findings using existing information from the USA and the United Kingdom. All the research that we are proposing will use pre-existing information or samples. How are we going to answer our research questions? To answer our research questions, we will use three different groups of people from: (1) Canada, (2) the USA, and (3) the United Kingdom. Study participants from the Canadian group have MS; or depression or anxiety without any immune disease; or are healthy people (in other words, no mental health disorders and no autoimmune diseases). The second group of participants is from the United States and were part of a clinical trial that was funded by the U.S. National Institutes of Health to study MS drugs. We will re-use this data, collected as part of the clinical trial, to answer our questions. The last group of participants is from the United Kingdom, as part of a large biobank study called UK Biobank. This is a very large study of over 500,000 individuals aged 37-73 years, with around 2,000 of them having MS. Very similar information on all three groups of participants was collected including: age, sex, cognitive functioning, other health conditions, and MS-specific measures, such as number of relapses. We will then calculate the mental health genetic score by first using a "training set" from publicly available data. The training set will then be applied to the test set, i.e., the participants from Canada, the USA, and the UK. We can then perform statistical modelling to answer our research questions. What types of patients will this research help, and how? We hope to help people with MS by identifying those who might be at high risk for a mental health disorder or very likely to have faster MS disease activity or MS disease progression or for cognitive impairment. The potential clinical applications are that by understanding if the mental health genetic scores are associated with a psychiatric disorder or with a poor outcome in MS, we could use these genetic scores as a clinical test to improve the identification of mental health disorders or of a poor outcome, leading to earlier treatment, thereby improving health outcomes for those with MS. This proposal will also further the current knowledge of the high rate of mental health disorde
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010566
Entities
People
- Kaarina Kowalec
Organizations
- United States Army
- University of Manitoba