TY - JOUR
T1 - Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
AU - Alzheimer's Disease Neuroimaging Initiative
AU - Hollingworth, Paul
AU - Harold, Denise
AU - Sims, Rebecca
AU - Gerrish, Amy
AU - Lambert, Jean-Charles
AU - Carrasquillo, Minerva M
AU - Abraham, Richard
AU - Hamshere, Marian L
AU - Pahwa, Jaspreet Singh
AU - Moskvina, Valentina
AU - Dowzell, Kimberley
AU - Jones, Nicola
AU - Stretton, Alexandra
AU - Thomas, Charlene
AU - Richards, Alex
AU - Ivanov, Dobril
AU - Widdowson, Caroline
AU - Chapman, Jade
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 - Brown, Kristelle S
AU - Passmore, Peter A
AU - Craig, David
AU - McGuinness, Bernadette
AU - Todd, Stephen
AU - Holmes, Clive
AU - Mann, David
AU - Smith, A David
AU - Beaumont, Helen
AU - Warden, Donald
AU - Wilcock, Gordon
AU - Love, Seth
AU - Kehoe, Patrick G
AU - Hooper, Nigel M
AU - Vardy, Emma R L C
AU - Hardy, John
AU - Mead, Simon
AU - Fox, Nick C
AU - Morris, John C
AU - Shaw, Christopher E
AU - Lopez, Oscar
AU - Jones, Lesley
AU - Morgan, Kevin
N1 - , Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom
PY - 2011/5
Y1 - 2011/5
N2 - We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
AB - We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
KW - ATP-Binding Cassette Transporters/genetics
KW - Adaptor Proteins, Signal Transducing/genetics
KW - Aged
KW - Aged, 80 and over
KW - Alzheimer Disease/genetics
KW - Antigens, CD/genetics
KW - Antigens, Differentiation, Myelomonocytic/genetics
KW - Case-Control Studies
KW - Cytoskeletal Proteins/genetics
KW - Databases, Genetic
KW - Female
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Membrane Proteins/genetics
KW - Multigene Family
KW - Polymorphism, Single Nucleotide
KW - Receptor, EphA1/genetics
KW - Sialic Acid Binding Ig-like Lectin 3
U2 - 10.1038/ng.803
DO - 10.1038/ng.803
M3 - Article
C2 - 21460840
SN - 1061-4036
VL - 43
SP - 429
EP - 435
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -