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

TitleGenetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
Publication TypeJournal Article
Year of Publication2015
AuthorsDesikan, RS, Schork, AJ, Wang, Y, Witoelar, A, Sharma, M, McEvoy, LK, Holland, D, Brewer, JB, Chen, C-H, Thompson, WK, Harold, D, Williams, J, Owen, MJ, O'Donovan, MC, Pericak-Vance, MA, Mayeux, R, Haines, JL, Farrer, LA, Schellenberg, GD, Heutink, P, Singleton, AB, Brice, A, Wood, NW, Hardy, J, Martinez, M, Choi, SH, DeStefano, A, Ikram, MA, Bis, JC, Smith, A, Fitzpatrick, AL, Launer, L, van Duijn, C, Seshadri, S, Ulstein, ID, Aarsland, D, Fladby, T, Djurovic, S, Hyman, BT, Snaedal, J, Stefansson, H, Stefansson, K, Gasser, T, Andreassen, OA, Dale, AM
Corporate AuthorsADNI, ADGC, GERAD, CHARGE and IPDGC Investigators
JournalMol Psychiatry
Volume20
Issue12
Pagination1588-95
Date Published2015 Dec
ISSN1476-5578
KeywordsAged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Chromosomes, Human, Pair 17, Female, Genetic Loci, Genetic Pleiotropy, Genome-Wide Association Study, Humans, Male, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, tau Proteins
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.

DOI10.1038/mp.2015.6
Alternate JournalMol. Psychiatry
PubMed ID25687773
PubMed Central IDPMC4539304
Grant ListR01 MH100351 / MH / NIMH NIH HHS / United States
MR/K013041/1 / / Medical Research Council / United Kingdom
P30 AG010124 / AG / NIA NIH HHS / United States
R01 AG031224 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
R01 GM104400 / GM / NIGMS NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
G-0907 / / Parkinson's UK / United Kingdom
K01AG029218 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
R01AG031224 / AG / NIA NIH HHS / United States
T32 EB005970 / EB / NIBIB NIH HHS / United States
U24-AG041689 / AG / NIA NIH HHS / United States
G0902227 / / Medical Research Council / United Kingdom
UL1 TR001108 / TR / NCATS NIH HHS / United States
MR/L501517/1 / / Medical Research Council / United Kingdom
K02NS067427 / NS / NINDS NIH HHS / United States
U24 AG041689 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
UO1AG032984 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
P50 AG025688 / AG / NIA NIH HHS / United States
K02 NS067427 / NS / NINDS NIH HHS / United States
R01 HD061414 / HD / NICHD NIH HHS / United States
MR/L010305/1 / / Medical Research Council / United Kingdom
R01HD061414 / HD / NICHD NIH HHS / United States
K01 AG029218 / AG / NIA NIH HHS / United States
RC2 DA029475 / DA / NIDA NIH HHS / United States
RC2DA029475 / DA / NIDA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States