Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
Title | Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Desikan, 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 Authors | ADNI, ADGC, GERAD, CHARGE and IPDGC Investigators |
Journal | Mol Psychiatry |
Volume | 20 |
Issue | 12 |
Pagination | 1588-95 |
Date Published | 2015 Dec |
ISSN | 1476-5578 |
Keywords | Aged, 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. |
DOI | 10.1038/mp.2015.6 |
Alternate Journal | Mol. Psychiatry |
PubMed ID | 25687773 |
PubMed Central ID | PMC4539304 |
Grant List | R01 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 |