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Desikan, R.S.* ; Schork, A.J.* ; Wang, Y.* ; Witoelar, A.W.* ; 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.* ; Singleton, A.B.* ; Brice, A.* ; Wood, N.W.* ; Hardy, J.* ; Martinez, M.* ; Choi, S.H.* ; DeStefano, A.L.* ; Ikram, M.A.* ; Bis, J.C.* ; Smith, A.* ; Fitzpatrick, A.L.* ; Launer, L.* ; van Duijn, C.M.* ; Seshadri, S* ; Ulstein, I.D.* ; Aarsland, D.* ; Fladby, T.* ; Djurovic, S.* ; Hyman, B.T.* ; Snaedal, J.* ; Stefansson, H.* ; Stefansson, K.* ; Gasser, T.* ; Andreassen, O.A.* ; Dale, A.M.* ; ADNI Investigators (*) ; ADGC Investigators (*) ; GERAD Investigators (*) ; CHARGE Investigators (*) ; IPDGC Investigators (Illig, T. ; Lichtner, P.)

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

Mol. Psychiatry 20, 1588-1595 (2015)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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 x 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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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Quellenangaben Volume: 20, Issue: 12, Pages: 1588-1595 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed