Michael J. Fox Foundation for Parkinson's Research

Leaps Project Title: High-Resolution Whole Genome Study to Determine Genetic Loci of Parkinson's Disease

We aim to identify susceptibility genes for Parkinson's disease (PD) by performing a genome-wide association study. We will genotype 200,000 SNPs in 500 sibpairs discordant for PD (affected individuals and their unaffected siblings). The 200,000 SNP markers that will be used in this initial screen have been selected because they are uniformly distributed across the genome and have allele frequencies greater than 10% in multiple populations making them a powerful reagent for whole genome association studies. The 2,000 markers having the most significant frequency differences between PD affected individuals and their unaffected siblings will be genotyped in an additional population consisting of 300 individuals with PD and 300 well-matched, unrelated controls. This two-tiered association study design will provide sufficient power (~80%) to identify all the major PD susceptibility genes and to identify risk factor profiles associated with a high risk for PD. The discovery of novel susceptibility genes will define pathogenesis pathways and provide new targets for disease modifying therapies. The end result will be pragmatic primary and secondary prevention strategies for PD.