Objective/Rationale:
The goal of this proposal is to analyze all available Parkinson’s disease (PD) genomewide association study (GWAS) datasets so that we can identify gene variants associated with the risk of PD. This information will then be used to recommend PD variants to be included on the ‘Neurochip,’ a new cross-disease DNA array which will be used in future clinical trials and genetic studies to better understand how genes may play roles in multiple diseases as well as provide personalized approaches for future therapies.
Project Description:
This project will review and analyze existing GWAS datasets from multiple investigators worldwide and use this large combined dataset to identify gene variants with the most definitive evidence for either increasing or decreasing the risk of PD. These variants will be combined with additional variants associated with drug response, ancestry informative markers and variants associated with the expression of genes in brain tissue. These will make up a set of important genetic markers that can be used when studying large numbers of subjects enrolling in clinical trials and new research studies.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
To date, researchers have sought to understand which genes affect PD risk. This study proposes to move past this question and identify DNA variants essential for a genetic profile obtained on all study subjects – those in research as well as those in clinical trials. Having such uniform data in thousands of subjects will allow us to understand whether a particular drug works best in individuals with particular genetic profiles.
Anticipated Outcome:
This study will have one critical outcome – the design of the PD portion of the ‘Neurochip’. The Neurochip is an NIH-sponsored effort bringing together researchers interested in many different neurological diseases to develop a DNA array that can be tested in hundreds of thousands of individuals involved in clinical trials and/or research. The goal will be not only the development of personalized medicine approaches but also the ability to explore whether certain genes are important across multiple neurological disorders.