Unraveling the Influence of Comorbidities on Parkinson’s Disease

Cassie Ramage

Mentor: Dr. Vanessa Pitz, Integrative Neurogenomics Unit, Laboratory of Neurogenetics and Center for Alzheimer’s and Related Dementias, National Institute on Aging, National Institutes of Health.

Date/Time: August 22nd, 2024 at 1:20pm.

Abstract: Parkinson’s Disease (PD) is a progressive neurological disorder impacting over 1% of older adults, significantly affecting motor function and overall quality of life. Our study explores the genetic interactions between PD and three common comorbidities: Depression (affecting 40-60% of PD patients), Type 2 Diabetes (20-30%), and Cardiovascular Disease (50%). Utilizing sequencing data from the UK Biobank and the All of Us Research Program, we performed Genome-Wide Association Studies (GWAS) with REGENIE to identify both rare (MAF < 0.01) and common (MAF > 0.01) genetic variants linked to PD and these comorbidities.

Our analysis identified several significant rare variants associated with each comorbidity in the individual datasets, including a notable common variant in the RAB6A gene within the Type 2 Diabetes cohort, which has been experimentally linked to disrupted neurite outgrowth. However, individual dataset analyses suffered from limited statistical power and genomic inflation, prompting us to conduct a meta-analysis to address these issues.

The meta-analysis reduced genomic inflation and improved statistical power but did not reveal significant SNPs across the combined datasets. This suggests that there may not be a strong genetic component contributing to the development of PD in individuals with these comorbidities, or vice versa.