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

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). [ABSTRACT FROM AUTHOR]