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


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.

SUBMITTER: Desikan RS 

PROVIDER: S-EPMC4539304 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Desikan R S RS   Schork A J AJ   Wang Y Y   Witoelar A A   Sharma M M   McEvoy L K LK   Holland D D   Brewer J B JB   Chen C-H CH   Thompson W K WK   Harold D D   Williams J J   Owen M J MJ   O'Donovan M C MC   Pericak-Vance M A MA   Mayeux R R   Haines J L JL   Farrer L A LA   Schellenberg G D GD   Heutink P P   Singleton A B AB   Brice A A   Wood N W NW   Hardy J J   Martinez M M   Choi S H SH   DeStefano A A   Ikram M A MA   Bis J C JC   Smith A A   Fitzpatrick A L AL   Launer L L   van Duijn C C   Seshadri S S   Ulstein I D ID   Aarsland D D   Fladby T T   Djurovic S S   Hyman B T BT   Snaedal J J   Stefansson H H   Stefansson K K   Gasser T T   Andreassen O A OA   Dale A M AM  

Molecular psychiatry 20150217 12


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 c  ...[more]

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