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 associat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797096062446469120 |
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| author | Hollingworth, P Harold, D Sims, R Gerrish, A Lambert, J Carrasquillo, M Abraham, R Hamshere, M Pahwa, J 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, M Brayne, C Rubinsztein, D Gill, M |
| author_facet | Hollingworth, P Harold, D Sims, R Gerrish, A Lambert, J Carrasquillo, M Abraham, R Hamshere, M Pahwa, J 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, M Brayne, C Rubinsztein, D Gill, M |
| author_sort | Hollingworth, P |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:36:43Z |
| format | Journal article |
| id | oxford-uuid:d02cf5bf-ffea-45c9-838d-2eff8b42ed7d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:36:43Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:d02cf5bf-ffea-45c9-838d-2eff8b42ed7d2022-03-27T07:48:12ZCommon variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d02cf5bf-ffea-45c9-838d-2eff8b42ed7dEnglishSymplectic Elements at Oxford2011Hollingworth, PHarold, DSims, RGerrish, ALambert, JCarrasquillo, MAbraham, RHamshere, MPahwa, JMoskvina, VDowzell, KJones, NStretton, AThomas, CRichards, AIvanov, DWiddowson, CChapman, JLovestone, SPowell, JProitsi, PLupton, MBrayne, CRubinsztein, DGill, MWe 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. |
| spellingShingle | Hollingworth, P Harold, D Sims, R Gerrish, A Lambert, J Carrasquillo, M Abraham, R Hamshere, M Pahwa, J 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, M Brayne, C Rubinsztein, D Gill, M Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title_full | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title_fullStr | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title_full_unstemmed | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title_short | Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease |
| title_sort | common variants at abca7 ms4a6a ms4a4e epha1 cd33 and cd2ap are associated with alzheimer s disease |
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