Study Rationale:
We previously showed that variants in two known Parkinson’s disease (PD) genes, LRRK2 and PARK16, genetically interact to increase risk of disease. Learning more about genetic variants associated with PD allows us to identify the biological pathways that may be disrupted in PD and that can be targeted with therapies.
Hypothesis:
We aim to replicate in different patient cohorts the finding that specific DNA variants in LRRK2 and PARK16 genetically interact to increase risk of disease.
Study Design:
First we will perform analysis of DNA variation at the LRRK2 and PARK16 genes using existing large datasets from both Ashkenazi Jewish populations and non-Jewish populations to show that there is a genetic interaction. Second, we will examine the clinical characteristics of patients who carry the interacting LRRK2 and PARK16 variants and patients who are non-carriers of these specific variants.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Confirming that these specific variants in LRRK2 and PARK16 interact to increase risk of Parkinson’s disease in other patient cohorts could have important implications for genetic testing and diagnosis. Additionally, modifying the gene expression signature associated with these risk DNA variants may be a potential therapeutic approach that could benefit patients.
Next Steps for Development:
If successful, this project will lead to development of disease models and therapeutics focused on LRRK2 and PARK16.