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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 ĝ‰Currency sign 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 ). © 2011 Nature America, Inc. All rights reserved.

Original publication

DOI

10.1038/ng.803

Type

Journal article

Journal

Nature Genetics

Publication Date

01/05/2011

Volume

43

Pages

429 - 436