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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 |