Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

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Title:	Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
Authors:	Desikan, R S, Schork, A J, Wang, Y, Witoelar, A, Sharma, M, McEvoy, L K, Holland, D, Brewer, J B, Chen, C-H, Thompson, W K, Harold, D, Williams, J, Owen, M J, O'Donovan, M C, Pericak-Vance, M A, Mayeux, R, Haines, J L, Farrer, L A, Schellenberg, G D, Heutink, P
Source:	Molecular Psychiatry. Dec2015, Vol. 20 Issue 12, p1588-1595. 8p.
Subjects:	Genetics of Alzheimer's disease, Parkinson's disease & genetics, Single nucleotide polymorphisms, Alleles, Neurodegeneration
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. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
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. [ABSTRACT FROM AUTHOR]
ISSN:	13594184
DOI:	10.1038/mp.2015.6