Objective/Rationale:
We propose to design and complete a collaborative study that will bring together data and samples from subjects with LRRK2 mutations with the express goal of identifying the genetic variants contributing to the variation in age of onset of PD in LRRK2 mutation carriers. We will complete an initial planning stage and then implementation and analysis phases to test the role of both common and rare variation.
Project Description:
The project is divided into 3 phases. The planning phase will be overseen by Indiana University staff who will coordinate all groups having samples and data from LRRK2 mutation carriers and develop a Memorandum of Understanding (MOU) to guide the collaborative study. In addition, an Analytic Group will develop an analysis plan for the genomewide SNP data. The implementation phase will consist of identifying all samples and then coordinating the shipment of these samples to a central location for plating and genotyping. The analysis phase will involve a team of analysts from the contributing research studies implementing the analytic plan developed in the planning phase. At the conclusion of the analysis phase, a meeting will be held to review the results and decide the scope and design of studies. This meeting will also be used to determine how a replication study might be designed and implemented.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The identification of these genetic factors will improve our understanding of the role of LRRK2 in PD in several ways. First, we hypothesize that the novel genes and DNA variants that are identified in this study will advance our understanding of the biological mechanisms of LRRK2. Second, these genetic factors may prove to be useful therapeutic targets that could be used to delay the onset of PD among those with LRRK2 mutations. Third, screening of these genetic variants could be included as part of LRRK2 genetic testing and results provided as part of the genetic counseling to yield better estimates of the likely onset of PD for a particular at-risk individual.
Anticipated Outcome:
The identification of these genetic factors will improve our understanding of the role of LRRK2 in PD in several ways. First, we hypothesize that the novel genes and DNA variants that are identified in this study will advance our understanding of the biological mechanisms of LRRK2. Second, these genetic factors may prove to be useful therapeutic targets that could be used to delay the onset of PD among those with LRRK2 mutations. Third, screening of these genetic variants could be included as part of LRRK2 genetic testing and results provided as part of the genetic counseling to yield better estimates of the likely onset of PD for a particular at-risk individual.