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

Desikan, R S, Schork, A J, Wang, Y, Witoelar, A, Sharma, M, McEvoy, L K, Holland, D, Brewer, J B, Chen, C-H, Thompson, W K, Harold, Denise, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, 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, Ikram, M A, Bis, J C, Smith, A, Fitzpatrick, A L, Launer, L, van Duijn, C, 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 and Dale, A M 2015. Genetic overlap between Alzheimer's Disease and Parkinson's Disease at the MAPT locus. Molecular Psychiatry 20 (12) , pp. 1588-1595. 10.1038/mp.2015.6

Full text not available from this repository.

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Date of Acceptance:	8 January 2015
Last Modified:	31 Oct 2022 10:24
URI:	https://orca.cardiff.ac.uk/id/eprint/84739

Citation Data

Cited 91 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item