Abstract
We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10 -7). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.
Original language | English (US) |
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Pages (from-to) | 1588-1595 |
Number of pages | 8 |
Journal | Molecular psychiatry |
Volume | 20 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2015 |
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience