Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
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AuthorsDesikan, R S
Schork, A J
McEvoy, L K
Brewer, J B
Thompson, W K
Owen, M J
O'Donovan, M C
Pericak-Vance, M A
Haines, J L
Farrer, L A
Schellenberg, G D
Singleton, A B
Wood, N W
Choi, S H
Ikram, M A
Bis, J C
Fitzpatrick, A L
van Duijn, C
Ulstein, I D
Hyman, B T
Andreassen, O A
Dale, A M
MetadataShow full item record
CitationGenetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. 2015, 20 (12):1588-95 Mol. Psychiatry
AbstractWe 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.
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