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Desikan, R.S. (R. S.), Schork, A.J. (A. J.), Wang, Y. (Y.), A. Witoelar (Aree), Sharma, M. (M.), McEvoy, L.K. (L. K.), Holland, D. (D.), Brewer, J.B. (J. B.), Chen, C.-H. (C. H.), Thompson, W.K. (W. K.), et al. D. Harold (Denise), Williams, J. (J.), M.J. Owen (Michael), M.C. O'donovan (Michael), M.A. Pericak-Vance (Margaret), Mayeux, R. (R.), J.L. Haines (Jonathan), L.A. Farrer (Lindsay), Schellenberg, G.D. (G. D.), P. Heutink (Peter), Singleton, A.B. (A. B.), Brice, A. (A.), Wood, N.W. (N. W.), Hardy, J. (J.), Martinez, M. (M.), S.-H. Choi (Seung-Hoan), Destefano, A. (A.), Ikram, M.A. (M. A.), J.C. Bis (Joshua), Smith, A. (A.), A.L. Fitzpatrick (Annette), L.J. Launer (Lenore), Van Duijn, C. (C.), Seshadri, S. (S.), I. Ulstein (Ingun), Aarsland, D. (D.), Fladby, T. (T.), S. Djurovic (Srdjan), B.T. Hyman (Bradley), J. SnÆdal (Jon), H. Stefansson (Hreinn), Stefansson, K. (K.), Gasser, T. (T.), Andreassen, O.A. (O. A.) and Dale, A.M. (A. M.)

2015

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

Publication

Publication

Molecular Psychiatry , Volume 20 - Issue 12 p. 1588- 1595

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.

Additional Metadata
Persistent URL doi.org/10.1038/mp.2015.6, hdl.handle.net/1765/79292
Journal Molecular Psychiatry
Organisation Department of Epidemiology
Citation
Desikan, R.S. (R. S.), Schork, A.J. (A. J.), Wang, Y. (Y.), Witoelar, A., Sharma, M. (M.), McEvoy, L.K. (L. K.), … Dale, A.M. (A. M.). (2015). Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Molecular Psychiatry, 20(12), 1588–1595. doi:10.1038/mp.2015.6
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