The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease.
Standard
The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease. / 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; Bussche van den, 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.
In: J ALZHEIMERS DIS, Vol. 28, No. 2, 2, 2012, p. 377-387.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease.
AU - Gerrish, Amy
AU - Russo, Giancarlo
AU - Richards, Alexander
AU - Moskvina, Valentina
AU - Ivanov, Dobril
AU - Harold, Denise
AU - Sims, Rebecca
AU - Abraham, Richard
AU - Hollingworth, Paul
AU - Chapman, Jade
AU - Hamshere, Marian
AU - Pahwa, Jaspreet Singh
AU - Dowzell, Kimberley
AU - Williams, Amy
AU - Jones, Nicola
AU - Thomas, Charlene
AU - Stretton, Alexandra
AU - Morgan, Angharad R
AU - Lovestone, Simon
AU - Powell, John
AU - Proitsi, Petroula
AU - Lupton, Michelle K
AU - Brayne, Carol
AU - Rubinsztein, David C
AU - Gill, Michael
AU - Lawlor, Brian
AU - Lynch, Aoibhinn
AU - Morgan, Kevin
AU - Brown, Kristelle S
AU - Passmore, Peter A
AU - Craig, David
AU - McGuinness, Bernadette
AU - Todd, Stephen
AU - Johnston, Janet A
AU - Holmes, Clive
AU - Mann, David
AU - Smith, A David
AU - Love, Seth
AU - Kehoe, Patrick G
AU - Hardy, John
AU - Mead, Simon
AU - Fox, Nick
AU - Rossor, Martin
AU - Collinge, John
AU - Maier, Wolfgang
AU - Jessen, Frank
AU - Kölsch, Heike
AU - Heun, Reinhard
AU - Schürmann, Britta
AU - Bussche van den, Hendrik
AU - Heuser, Isabella
AU - Kornhuber, Johannes
AU - Wiltfang, Jens
AU - Dichgans, Martin
AU - Frölich, Lutz
AU - Hampel, Harald
AU - Hüll, Michael
AU - Rujescu, Dan
AU - Goate, Alison M
AU - Kauwe, John S K
AU - Cruchaga, Carlos
AU - Nowotny, Petra
AU - Morris, John C
AU - Mayo, Kevin
AU - Livingston, Gill
AU - Bass, Nicholas J
AU - Gurling, Hugh
AU - McQuillin, Andrew
AU - Gwilliam, Rhian
AU - Deloukas, Panagiotis
AU - Davies, Gail
AU - Harris, Sarah E
AU - Starr, John M
AU - Deary, Ian J
AU - Al-Chalabi, Ammar
AU - Shaw, Christopher E
AU - Tsolaki, Magda
AU - Singleton, Andrew B
AU - Guerreiro, Rita
AU - Mühleisen, Thomas W
AU - Nöthen, Markus M
AU - Moebus, Susanne
AU - Jöckel, Karl-Heinz
AU - Klopp, Norman
AU - Wichmann, H-Erich
AU - Carrasquillo, Minerva M
AU - Pankratz, V Shane
AU - Younkin, Steven G
AU - Jones, Lesley
AU - Holmans, Peter A
AU - O'Donovan, Michael C
AU - Owen, Michael J
AU - Williams, Julie
PY - 2012
Y1 - 2012
N2 - Rare mutations in A?PP, 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 A?PP, 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.
AB - Rare mutations in A?PP, 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 A?PP, 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.
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Aged, 80 and over
KW - Meta-Analysis as Topic
KW - Genotype
KW - Odds Ratio
KW - Genome-Wide Association Study
KW - Alzheimer Disease/genetics
KW - Polymorphism, Single Nucleotide/genetics
KW - Genetic Predisposition to Disease
KW - Amyloid beta-Protein Precursor/genetics
KW - Presenilin-1/genetics
KW - Presenilin-2/genetics
KW - tau Proteins/genetics
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Aged, 80 and over
KW - Meta-Analysis as Topic
KW - Genotype
KW - Odds Ratio
KW - Genome-Wide Association Study
KW - Alzheimer Disease/genetics
KW - Polymorphism, Single Nucleotide/genetics
KW - Genetic Predisposition to Disease
KW - Amyloid beta-Protein Precursor/genetics
KW - Presenilin-1/genetics
KW - Presenilin-2/genetics
KW - tau Proteins/genetics
M3 - SCORING: Journal article
VL - 28
SP - 377
EP - 387
JO - J ALZHEIMERS DIS
JF - J ALZHEIMERS DIS
SN - 1387-2877
IS - 2
M1 - 2
ER -