Journal of Alzheimer's disease : JAD · 2012

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Gerrish Amy, Russo Giancarlo, Richards Alexander, Moskvina Valentina, Ivanov Dobril, Harold Denise, Sims Rebecca, Abraham Richard, Hollingworth Paul, Chapman Jade, Hamshere Marian, Pahwa Jaspreet Singh, Dowzell Kimberley, Williams Amy, Jones Nicola, Thomas Charlene, Stretton Alexandra, Morgan Angharad R, 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 A, O'Donovan Michael C, Owen Michael J, Williams Julie

Аннотация

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.

Предметные рубрики MeSH

Aged Aged, 80 and over Alzheimer Disease Amyloid beta-Protein Precursor Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Male Meta-Analysis as Topic Odds Ratio Polymorphism, Single Nucleotide Presenilin-1 Presenilin-2 tau Proteins

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH