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

2.50
Hdl Handle:
http://hdl.handle.net/2336/225681
Title:
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
Authors:
Hollingworth, Paul; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Lambert, Jean-Charles; Carrasquillo, Minerva M; Abraham, Richard; Hamshere, Marian L; Pahwa, Jaspreet Singh; Moskvina, Valentina; Dowzell, Kimberley; Jones, Nicola; Stretton, Alexandra; Thomas, Charlene; Richards, Alex; Ivanov, Dobril; Widdowson, Caroline; Chapman, Jade; Lovestone, Simon; Powell, John; Proitsi, Petroula; Lupton, Michelle K; Brayne, Carol; Rubinsztein, David C; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Brown, Kristelle S; Passmore, Peter A; Craig, David; McGuinness, Bernadette; Todd, Stephen; Holmes, Clive; Mann, David; Smith, A David; Beaumont, Helen; Warden, Donald; Wilcock, Gordon; Love, Seth; Kehoe, Patrick G; Hooper, Nigel M; Vardy, Emma R L C; Hardy, John; Mead, Simon; Fox, Nick C; Rossor, Martin; Collinge, John; Maier, Wolfgang; Jessen, Frank; Rüther, Eckart; Schürmann, Britta; Heun, Reiner; Kölsch, Heike; van den Bussche, Hendrik; Heuser, Isabella; Kornhuber, Johannes; Wiltfang, Jens; Dichgans, Martin; Frölich, Lutz; Hampel, Harald; Gallacher, John; Hüll, Michael; Rujescu, Dan; Giegling, Ina; Goate, Alison M; Kauwe, John S K; Cruchaga, Carlos; Nowotny, Petra; Morris, John C; Mayo, Kevin; Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter P; Van Broeckhoven, Christine; Livingston, Gill; Bass, Nicholas J; Gurling, Hugh; McQuillin, Andrew; Gwilliam, Rhian; Deloukas, Panagiotis; Al-Chalabi, Ammar; Shaw, Christopher E; Tsolaki, Magda; Singleton, Andrew B; Guerreiro, Rita; Mühleisen, Thomas W; Nöthen, Markus M; Moebus, Susanne; Jöckel, Karl-Heinz; Klopp, Norman; Wichmann, H-Erich; Pankratz, V Shane; Sando, Sigrid B; Aasly, Jan O; Barcikowska, Maria; Wszolek, Zbigniew K; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; van Duijn, Cornelia M; Breteler, Monique M B; Ikram, M Arfan; DeStefano, Anita L; Fitzpatrick, Annette L; Lopez, Oscar; Launer, Lenore J; Seshadri, Sudha; Berr, Claudine; Campion, Dominique; Epelbaum, Jacques; Dartigues, Jean-François; Tzourio, Christophe; Alpérovitch, Annick; Lathrop, Mark; Feulner, Thomas M; Friedrich, Patricia; Riehle, Caterina; Krawczak, Michael; Schreiber, Stefan; Mayhaus, Manuel; Nicolhaus, S; Wagenpfeil, Stefan; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari; Snaedal, Jon; Björnsson, Sigurbjörn; Jonsson, Palmi V; Chouraki, Vincent; Genier-Boley, Benjamin; Hiltunen, Mikko; Soininen, Hilkka; Combarros, Onofre; Zelenika, Diana; Delepine, Marc; Bullido, Maria J; Pasquier, Florence; Mateo, Ignacio; Frank-Garcia, Ana; Porcellini, Elisa; Hanon, Olivier; Coto, Eliecer; Alvarez, Victoria; Bosco, Paolo; Siciliano, Gabriele; Mancuso, Michelangelo; Panza, Francesco; Solfrizzi, Vincenzo; Nacmias, Benedetta; Sorbi, Sandro; Bossù, Paola; Piccardi, Paola; Arosio, Beatrice; Annoni, Giorgio; Seripa, Davide; Pilotto, Alberto; Scarpini, Elio; Galimberti, Daniela; Brice, Alexis; Hannequin, Didier; Licastro, Federico; Jones, Lesley; Holmans, Peter A; Jonsson, Thorlakur; Riemenschneider, Matthias; Morgan, Kevin; Younkin, Steven G; Owen, Michael J; O'Donovan, Michael; Amouyel, Philippe; Williams, Julie
Citation:
Nat. Genet. 2011, 43(5):429-35
Issue Date:
May-2011
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)).
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084173/pdf/ukmss-34702.pdf
Rights:
Archived with thanks to Nature genetics

Full metadata record

DC FieldValue Language
dc.contributor.authorHollingworth, Paulen_GB
dc.contributor.authorHarold, Deniseen_GB
dc.contributor.authorSims, Rebeccaen_GB
dc.contributor.authorGerrish, Amyen_GB
dc.contributor.authorLambert, Jean-Charlesen_GB
dc.contributor.authorCarrasquillo, Minerva Men_GB
dc.contributor.authorAbraham, Richarden_GB
dc.contributor.authorHamshere, Marian Len_GB
dc.contributor.authorPahwa, Jaspreet Singhen_GB
dc.contributor.authorMoskvina, Valentinaen_GB
dc.contributor.authorDowzell, Kimberleyen_GB
dc.contributor.authorJones, Nicolaen_GB
dc.contributor.authorStretton, Alexandraen_GB
dc.contributor.authorThomas, Charleneen_GB
dc.contributor.authorRichards, Alexen_GB
dc.contributor.authorIvanov, Dobrilen_GB
dc.contributor.authorWiddowson, Carolineen_GB
dc.contributor.authorChapman, Jadeen_GB
dc.contributor.authorLovestone, Simonen_GB
dc.contributor.authorPowell, Johnen_GB
dc.contributor.authorProitsi, Petroulaen_GB
dc.contributor.authorLupton, Michelle Ken_GB
dc.contributor.authorBrayne, Carolen_GB
dc.contributor.authorRubinsztein, David Cen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorLawlor, Brianen_GB
dc.contributor.authorLynch, Aoibhinnen_GB
dc.contributor.authorBrown, Kristelle Sen_GB
dc.contributor.authorPassmore, Peter Aen_GB
dc.contributor.authorCraig, Daviden_GB
dc.contributor.authorMcGuinness, Bernadetteen_GB
dc.contributor.authorTodd, Stephenen_GB
dc.contributor.authorHolmes, Cliveen_GB
dc.contributor.authorMann, Daviden_GB
dc.contributor.authorSmith, A Daviden_GB
dc.contributor.authorBeaumont, Helenen_GB
dc.contributor.authorWarden, Donalden_GB
dc.contributor.authorWilcock, Gordonen_GB
dc.contributor.authorLove, Sethen_GB
dc.contributor.authorKehoe, Patrick Gen_GB
dc.contributor.authorHooper, Nigel Men_GB
dc.contributor.authorVardy, Emma R L Cen_GB
dc.contributor.authorHardy, Johnen_GB
dc.contributor.authorMead, Simonen_GB
dc.contributor.authorFox, Nick Cen_GB
dc.contributor.authorRossor, Martinen_GB
dc.contributor.authorCollinge, Johnen_GB
dc.contributor.authorMaier, Wolfgangen_GB
dc.contributor.authorJessen, Franken_GB
dc.contributor.authorRüther, Eckarten_GB
dc.contributor.authorSchürmann, Brittaen_GB
dc.contributor.authorHeun, Reineren_GB
dc.contributor.authorKölsch, Heikeen_GB
dc.contributor.authorvan den Bussche, Hendriken_GB
dc.contributor.authorHeuser, Isabellaen_GB
dc.contributor.authorKornhuber, Johannesen_GB
dc.contributor.authorWiltfang, Jensen_GB
dc.contributor.authorDichgans, Martinen_GB
dc.contributor.authorFrölich, Lutzen_GB
dc.contributor.authorHampel, Haralden_GB
dc.contributor.authorGallacher, Johnen_GB
dc.contributor.authorHüll, Michaelen_GB
dc.contributor.authorRujescu, Danen_GB
dc.contributor.authorGiegling, Inaen_GB
dc.contributor.authorGoate, Alison Men_GB
dc.contributor.authorKauwe, John S Ken_GB
dc.contributor.authorCruchaga, Carlosen_GB
dc.contributor.authorNowotny, Petraen_GB
dc.contributor.authorMorris, John Cen_GB
dc.contributor.authorMayo, Kevinen_GB
dc.contributor.authorSleegers, Kristelen_GB
dc.contributor.authorBettens, Karolienen_GB
dc.contributor.authorEngelborghs, Sebastiaanen_GB
dc.contributor.authorDe Deyn, Peter Pen_GB
dc.contributor.authorVan Broeckhoven, Christineen_GB
dc.contributor.authorLivingston, Gillen_GB
dc.contributor.authorBass, Nicholas Jen_GB
dc.contributor.authorGurling, Hughen_GB
dc.contributor.authorMcQuillin, Andrewen_GB
dc.contributor.authorGwilliam, Rhianen_GB
dc.contributor.authorDeloukas, Panagiotisen_GB
dc.contributor.authorAl-Chalabi, Ammaren_GB
dc.contributor.authorShaw, Christopher Een_GB
dc.contributor.authorTsolaki, Magdaen_GB
dc.contributor.authorSingleton, Andrew Ben_GB
dc.contributor.authorGuerreiro, Ritaen_GB
dc.contributor.authorMühleisen, Thomas Wen_GB
dc.contributor.authorNöthen, Markus Men_GB
dc.contributor.authorMoebus, Susanneen_GB
dc.contributor.authorJöckel, Karl-Heinzen_GB
dc.contributor.authorKlopp, Normanen_GB
dc.contributor.authorWichmann, H-Erichen_GB
dc.contributor.authorPankratz, V Shaneen_GB
dc.contributor.authorSando, Sigrid Ben_GB
dc.contributor.authorAasly, Jan Oen_GB
dc.contributor.authorBarcikowska, Mariaen_GB
dc.contributor.authorWszolek, Zbigniew Ken_GB
dc.contributor.authorDickson, Dennis Wen_GB
dc.contributor.authorGraff-Radford, Neill Ren_GB
dc.contributor.authorPetersen, Ronald Cen_GB
dc.contributor.authorvan Duijn, Cornelia Men_GB
dc.contributor.authorBreteler, Monique M Ben_GB
dc.contributor.authorIkram, M Arfanen_GB
dc.contributor.authorDeStefano, Anita Len_GB
dc.contributor.authorFitzpatrick, Annette Len_GB
dc.contributor.authorLopez, Oscaren_GB
dc.contributor.authorLauner, Lenore Jen_GB
dc.contributor.authorSeshadri, Sudhaen_GB
dc.contributor.authorBerr, Claudineen_GB
dc.contributor.authorCampion, Dominiqueen_GB
dc.contributor.authorEpelbaum, Jacquesen_GB
dc.contributor.authorDartigues, Jean-Françoisen_GB
dc.contributor.authorTzourio, Christopheen_GB
dc.contributor.authorAlpérovitch, Annicken_GB
dc.contributor.authorLathrop, Marken_GB
dc.contributor.authorFeulner, Thomas Men_GB
dc.contributor.authorFriedrich, Patriciaen_GB
dc.contributor.authorRiehle, Caterinaen_GB
dc.contributor.authorKrawczak, Michaelen_GB
dc.contributor.authorSchreiber, Stefanen_GB
dc.contributor.authorMayhaus, Manuelen_GB
dc.contributor.authorNicolhaus, Sen_GB
dc.contributor.authorWagenpfeil, Stefanen_GB
dc.contributor.authorSteinberg, Stacyen_GB
dc.contributor.authorStefansson, Hreinnen_GB
dc.contributor.authorStefansson, Karien_GB
dc.contributor.authorSnaedal, Jonen_GB
dc.contributor.authorBjörnsson, Sigurbjörnen_GB
dc.contributor.authorJonsson, Palmi Ven_GB
dc.contributor.authorChouraki, Vincenten_GB
dc.contributor.authorGenier-Boley, Benjaminen_GB
dc.contributor.authorHiltunen, Mikkoen_GB
dc.contributor.authorSoininen, Hilkkaen_GB
dc.contributor.authorCombarros, Onofreen_GB
dc.contributor.authorZelenika, Dianaen_GB
dc.contributor.authorDelepine, Marcen_GB
dc.contributor.authorBullido, Maria Jen_GB
dc.contributor.authorPasquier, Florenceen_GB
dc.contributor.authorMateo, Ignacioen_GB
dc.contributor.authorFrank-Garcia, Anaen_GB
dc.contributor.authorPorcellini, Elisaen_GB
dc.contributor.authorHanon, Olivieren_GB
dc.contributor.authorCoto, Elieceren_GB
dc.contributor.authorAlvarez, Victoriaen_GB
dc.contributor.authorBosco, Paoloen_GB
dc.contributor.authorSiciliano, Gabrieleen_GB
dc.contributor.authorMancuso, Michelangeloen_GB
dc.contributor.authorPanza, Francescoen_GB
dc.contributor.authorSolfrizzi, Vincenzoen_GB
dc.contributor.authorNacmias, Benedettaen_GB
dc.contributor.authorSorbi, Sandroen_GB
dc.contributor.authorBossù, Paolaen_GB
dc.contributor.authorPiccardi, Paolaen_GB
dc.contributor.authorArosio, Beatriceen_GB
dc.contributor.authorAnnoni, Giorgioen_GB
dc.contributor.authorSeripa, Davideen_GB
dc.contributor.authorPilotto, Albertoen_GB
dc.contributor.authorScarpini, Elioen_GB
dc.contributor.authorGalimberti, Danielaen_GB
dc.contributor.authorBrice, Alexisen_GB
dc.contributor.authorHannequin, Didieren_GB
dc.contributor.authorLicastro, Federicoen_GB
dc.contributor.authorJones, Lesleyen_GB
dc.contributor.authorHolmans, Peter Aen_GB
dc.contributor.authorJonsson, Thorlakuren_GB
dc.contributor.authorRiemenschneider, Matthiasen_GB
dc.contributor.authorMorgan, Kevinen_GB
dc.contributor.authorYounkin, Steven Gen_GB
dc.contributor.authorOwen, Michael Jen_GB
dc.contributor.authorO'Donovan, Michaelen_GB
dc.contributor.authorAmouyel, Philippeen_GB
dc.contributor.authorWilliams, Julieen_GB
dc.date.accessioned2012-05-24T11:43:06Z-
dc.date.available2012-05-24T11:43:06Z-
dc.date.issued2011-05-
dc.identifier.citationNat. Genet. 2011, 43(5):429-35en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid21460840-
dc.identifier.doi10.1038/ng.803-
dc.identifier.urihttp://hdl.handle.net/2336/225681-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractWe 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)).en_GB
dc.description.sponsorshipWellcome Trust Medical Research Council (UK) Alzheimer's Research UK Welsh Assembly Government Mercer's Institute for Research on Ageing Alzheimer's Society Ulster Garden Villages Northern Ireland RD Office Royal College of Physicians Dunhill Medical Trust Bristol Research into Alzheimer's and Care of the Eldery US National Institutes of Health Barnes Jewish Foundation Charles and Joanne Knight Alzheimer's Research Initiative University College London (UCL) Hospital/UCL Biomedical Centre Lundbeck German Federal Ministry of Education and Research Competence Network Dementia and Competence Network Degenerative Dementia Alfried Krupp von Bohlen und Halbach-Stiftung National Institute of Ageing Department of Health and Human Services University of Antwerp Fund for Scientific Research-Flanders Foundation for Alzheimer Research Methusalem Excellence grant Federal Science Policy Office Mayo AD Research Center National Institute of Neurological Disorders and Stroke Robert and Clarice Smith Postdoctoral Fellowship and AD Research Program Palumbo Professorship in AD Research Carl Edward and Susan Bass Bolch Gift Institut Pasteur de Lille Centre National de Genotypage Fondation pour la Recherche Medicale Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sant Institut de la Longevite Agence Francaise de Securite Sanitaire des Produits de Sante Aquitaine and Bourgogne Regional Councils Fondation de France French Ministry of Research/Institute national de la sante et de la recherche medicale Eisai Health Research Council of the Academy of Finland Nordic Centre of Excellence in Neurodegeneration Italian Ministry of Research Carimonte Foundation Italian Ministry of Health Fondazione Monzino Ministerio de Educacion y Ciencia the Ministerio de Sanidad y Consumo Fundacion Ramon Areces National Institute of Biomedical Imaging Bioengineering Abbott AstraZeneca Bayer Schering Pharma Bristol-Myers Squibb Elan Genentech GE GlaxoSmithKline Innogenetics Johnson and Johnson Eli Lilly Medpace Merck Novartis Pfizer Hoffman-La Roche Schering-Plough Synarc Wyeth Alzheimer's Association Alzheimer's Drug Discovery Foundation US Food and Drug Administration Foundation for the National Institutes of Health Northern California Institute for Research and Education Dana Foundation German National Genome Research Network German Ministry for Education and Research National Institute on Deafness and Other Communication Disorders Hjartavernd Althingi National Heart Lung and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Robert Dawson Evans Endowment Netherlands Organisation of Scientific Research Netherlands Genomics Initiative Erasmus Medical Center Netherlands organization for scientific research Netherlands Organization for the Health Research and Development Research Institute for Diseases in the Elderly Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission Municipality of Rotterdam NIHR Biomedical Research Centre, Oxford Health Foundationen_GB
dc.language.isoenen
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084173/pdf/ukmss-34702.pdfen_GB
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subject.meshATP-Binding Cassette Transportersen_GB
dc.subject.meshAdaptor Proteins, Signal Transducingen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshAlzheimer Diseaseen_GB
dc.subject.meshAntigens, CDen_GB
dc.subject.meshAntigens, Differentiation, Myelomonocyticen_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshCytoskeletal Proteinsen_GB
dc.subject.meshDatabases, Geneticen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshGenetic Variationen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMembrane Proteinsen_GB
dc.subject.meshMultigene Familyen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshReceptor, EphA1en_GB
dc.titleCommon variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.en
dc.typeArticleen
dc.contributor.departmentMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.en_GB
dc.identifier.journalNature geneticsen_GB

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