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Titel:

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

Dokumenttyp:
Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Article
Autor(en):
Hollingworth, P; Harold, D; Sims, R; Gerrish, A; Lambert, JC; Carrasquillo, MM; Abraham, R; Hamshere, ML; Pahwa, JS; Moskvina, V; Dowzell, K; Jones, N; Stretton, A; Thomas, C; Richards, A; Ivanov, D; Widdowson, C; Chapman, J; Lovestone, S; Powell, J; Proitsi, P; Lupton, MK; Brayne, C; Rubinsztein, DC; Gill, M; Lawlor, B; Lynch, A; Brown, KS; Passmore, PA; Craig, D; McGuinness, B; Todd, S; Holmes, C; Mann, D; Smith, AD; Beaumont, H; Warden, D; Wilcock, G; Love, S; Kehoe, PG; Hooper, NM; Vardy, ER...     »
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)).
Zeitschriftentitel:
Nat Genet
Jahr:
2011
Band / Volume:
43
Heft / Issue:
5
Seitenangaben Beitrag:
429-35
Sprache:
eng
Volltext / DOI:
doi:10.1038/ng.803
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/21460840
Print-ISSN:
1061-4036
TUM Einrichtung:
Institut für Medizinische Statistik und Epidemiologie
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