Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's Disease

Gerrish, Amy, Russo, Giancarlo, Richards, Alexander, Escott-Price, Valentina, Ivanov, Dobril, Harold, Denise, Sims, Rebecca, Abraham, Richard Alun, Hollingworth, Paul, Chapman, Jade Alice, Hamshere, Marian Lindsay, Pahwa, Jaspreet Singh, Dowzell, Kimberley Frances, Williams, Amy, Denning, Nicola, Thomas, Charlene, Stretton, Alexandra, Morgan, Angharad Rhys, Lovestone, Simon, Powell, John, Proitsi, Petroula, Lupton, Michelle K., Brayne, Carol, Rubinsztein, David C., Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Morgan, Kevin, Brown, Kristelle S., Passmore, Peter A., Craig, David, McGuinness, Bernadette, Todd, Stephen, Johnston, Janet A., Holmes, Clive, Mann, David, Smith, A. David, Love, Seth, Kehoe, Patrick G., Hardy, John, Mead, Simon, Fox, Nick, Rossor, Martin, Collinge, John, Maier, Wolfgang, Jessen, Frank, Kölsch, Heike, Heun, Reinhard, Schürmann, Britta, van den Bussche, Hendrik, Heuser, Isabella, Kornhuber, Johannes, Wiltfang, Jens, Dichgans, Martin, Frölich, Lutz, Hampel, Harald, Hüll, Michael, Rujescu, Dan, Goate, Alison M., Kauwe, John S. K., Cruchaga, Carlos, Nowotny, Petra, Morris, John C., Mayo, Kevin, Livingston, Gill, Bass, Nicholas J., Gurling, Hugh, McQuillin, Andrew, Gwilliam, Rhian, Deloukas, Panagiotis, Davies, Gail, Harris, Sarah E., Starr, John M., Deary, Ian J., Al-Chalabi, Ammar, Shaw, Christopher E., Tsolaki, Magda, Singleton, Andrew B., Guerreiro, Rita, Mühleisen, Thomas W., Nöthen, Markus M., Moebus, Susanne, Jöckel, Karl-Heinz, Klopp, Norman, Wichmann, H-Erich, Carrasquillo, Minerva M, Pankratz, V. Shane, Younkin, Steven G., Jones, Lesley, Holmans, Peter Alan, O'Donovan, Michael Conlon, Owen, Michael John and Williams, Julie 2012. The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's Disease. Journal of Alzheimer's Disease 28 (2) , pp. 377-387. 10.3233/JAD-2011-110824

Full text not available from this repository.

Abstract

Rare mutations in AβPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at AβPP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Alzheimer's disease, amyloid-β protein precursor, genetics, human, MAPT protein, PSEN1 protein, PSEN2 protein
Publisher: IOS Press
ISSN: 1875-8908
Last Modified: 08 May 2019 21:28
URI: http://orca.cf.ac.uk/id/eprint/29087

Citation Data

Cited 45 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item