Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

TitleCommon variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2011
AuthorsHollingworth P, Harold D, Sims R, Gerrish A, Lambert J-C, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JSingh, Moskvina V et al.
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative, CHARGE consortium, EADI1 consortium
JournalNat Genet
Volume43
Issue5
Pagination429-35
Date Published2011 May
ISSN1546-1718
KeywordsAdaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Alzheimer Disease, Antigens, CD, Antigens, Differentiation, Myelomonocytic, ATP-Binding Cassette Transporters, Case-Control Studies, Cytoskeletal Proteins, Databases, Genetic, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Multigene Family, Polymorphism, Single Nucleotide, Receptor, EphA1, Sialic Acid Binding Ig-like Lectin 3
Abstract

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)).

DOI10.1038/ng.803
Alternate JournalNat. Genet.
PubMed ID21460840
PubMed Central IDPMC3084173
Grant ListG0801306 / / Medical Research Council / United Kingdom
U24 AG021886 / AG / NIA NIH HHS / United States
G0802189 / / Medical Research Council / United Kingdom
MC_U123160651 / / Medical Research Council / United Kingdom
G0701075 / / Medical Research Council / United Kingdom
U19 AG010483 / AG / NIA NIH HHS / United States
/ / Medical Research Council / United Kingdom
G0300429 / / Medical Research Council / United Kingdom
082604 / / Wellcome Trust / United Kingdom
G0902227 / / Medical Research Council / United Kingdom
G0900688 / / Medical Research Council / United Kingdom
G0601846 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
G9810900 / / Medical Research Council / United Kingdom
MC_G1000734 / / Medical Research Council / United Kingdom