The Five Dimensions of Parkinson's Disease Genetic Risk

Genome-wide association studies of Parkinson's disease have revealed polymorphic variants associated with closely mapped genes of interest. We propose here that those genes may only represent the tip of an iceberg of regulatory effects and do not necessary reflect disease relevance. To usefully interpret a risk locus, one needs to consider 5 dimensions of information, which represent the three-dimensional structure of chromatin (dimensions #1- 3), which is locally variable across time (dimension #4), and, most importantly, dependent on cell type and context (dimension #5).