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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 publication

DOI

10.1038/mp.2015.6

Type

Journal article

Journal

Mol Psychiatry

Publication Date

12/2015

Volume

20

Pages

1588 - 1595

Keywords

Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Chromosomes, Human, Pair 17, Female, Genetic Loci, Genetic Pleiotropy, Genome-Wide Association Study, Humans, Male, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, tau Proteins