Description
- Abstract:
- Parkinson’s Disease (PD) is the second most prevalent neurodegenerative disorder following Alzheimer’s disease. By the time motor symptoms manifest, a significant proportion of nigrostriatal neurons has been lost due to degeneration. Better ways of early detection of high-risk individuals are needed, as these individuals can be targeted for PD clinical trials and future disease-modifying therapies. Polygenic risk score (PRS) models sum the contribution of multiple genetic risk variants of variable effect sizes to represent an individual’s genetic risk score for a disease. In PD, PRS has shown potential in predicting PD risk, age at onset, and progression of cognitive and motor symptoms. The association between PD PRS and other disease-specific subclinical traits, such as neuroimaging phenotypes, remains to be explored. In this study, we included 104 PD patients and 85 controls from the Parkinson’s Progression Markers Initiative (PPMI) dataset with available genotype and MRI Brain data. PRS was calculated using PRSice-2 software. Genetic variants were included based on their contribution to the risk of PD. The best p-value threshold was chosen based on comparing our PD patients to the healthy controls. T1-weighted MRI brains acquired on 3T scanners were processed using a fully-automated image analysis software, FreeSurfer (https://surfer.nmr.mgh.harvard.edu/). Volumetric measures of key brain regions were extracted, including the basal ganglia structures, thalamus, hippocampus, and amygdala (see Figure 2). Structure volumes were divided into contralateral and ipsilateral based on the patient’s motor symptoms dominance. Multiple linear regression models applied to examine the association between PD PRS and MRI-based brain structural volumes, while controlling for relevant covariates (e.g. age, gender, intracranial volume, and Hoehn and Yahr stage). The results showed that in de novo PD, PD PRS is associated with a smaller contralateral putamen volume (p=0.03). This finding highlights the relevant relationship between PD genetic risk variants and the putamen, a key brain structure associated with PD pathological mechanisms. This study was limited by a small sample and thus replication of our findings in a larger PD sample is warranted.
- Notes:
- Scholarly concentration: Non-Scholarly Concentrator
Access Conditions
- Use and Reproduction
- All rights reserved
- Rights
- In Copyright
- Restrictions on Use
- All Rights Reserved
Citation
Madour, Joseph, Brennan, Michael, Theriault, Harrison, et al.,
"The Association Between Parkinson’s Disease Brain Imaging Phenotypes and Common Genetic Variants: A Polygenic Risk Score Approach"
(2023).
Warren Alpert Medical School Academic Symposium.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:qvmv6hgn/
Relations
Collection:
-
Warren Alpert Medical School Academic Symposium
The Warren Alpert Medical School Academic Symposium is an annual event at Warren Alpert Medical School of Brown University that provides Year II medical students a venue to present their summer research in a poster format. Participation in the Symposium …...