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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)

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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 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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