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dc.contributor.authorTraylor, Matthew
dc.contributor.authorFarrall, Martin
dc.contributor.authorHolliday, Elizabeth G
dc.contributor.authorSudlow, Cathie
dc.contributor.authorHopewell, Jemma C
dc.contributor.authorCheng, Yu-Ching
dc.contributor.authorFornage, Myriam
dc.contributor.authorIkram, M Arfan
dc.contributor.authorMalik, Rainer
dc.contributor.authorBevan, Steve
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorNalls, Mike A
dc.contributor.authorLongstreth, WT
dc.contributor.authorWiggins, Kerri L
dc.contributor.authorYadav, Sunaina
dc.contributor.authorParati, Eugenio A
dc.contributor.authorDeStefano, Anita L
dc.contributor.authorWorrall, Bradford B
dc.contributor.authorKittner, Steven J
dc.contributor.authorKhan, Muhammad Saleem
dc.contributor.authorReiner, Alex P
dc.contributor.authorHelgadottir, Anna
dc.contributor.authorAchterberg, Sefanja
dc.contributor.authorFernandez-Cadenas, Israel
dc.contributor.authorAbboud, Sherine
dc.contributor.authorSchmidt, Reinhold
dc.contributor.authorWalters, Matthew
dc.contributor.authorChen, Wei-Min
dc.contributor.authorRingelstein, E Bernd
dc.contributor.authorO'Donnell, Martin
dc.contributor.authorHo, Weang Kee
dc.contributor.authorPera, Joanna
dc.contributor.authorLemmens, Robin
dc.contributor.authorNorrving, Bo
dc.contributor.authorHiggins, Peter
dc.contributor.authorBenn, Marianne
dc.contributor.authorSale, Michele
dc.contributor.authorKuhlenbäumer, Gregor
dc.contributor.authorDoney, Alexander S F
dc.contributor.authorVicente, Astrid M
dc.contributor.authorDelavaran, Hossein
dc.contributor.authorAlgra, Ale
dc.contributor.authorDavies, Gail
dc.contributor.authorOliveira, Sofia A
dc.contributor.authorPalmer, Colin N A
dc.contributor.authorDeary, Ian
dc.contributor.authorSchmidt, Helena
dc.contributor.authorPandolfo, Massimo
dc.contributor.authorMontaner, Joan
dc.contributor.authorCarty, Cara
dc.contributor.authorde Bakker, Paul I W
dc.contributor.authorKostulas, Konstantinos
dc.contributor.authorFerro, Jose M
dc.contributor.authorvan Zuydam, Natalie R
dc.contributor.authorValdimarsson, Einar
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorLindgren, Arne
dc.contributor.authorThijs, Vincent
dc.contributor.authorSlowik, Agnieszka
dc.contributor.authorSaleheen, Danish
dc.contributor.authorParé, Guillaume
dc.contributor.authorBerger, Klaus
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorHofman, Albert
dc.contributor.authorMosley, Thomas H
dc.contributor.authorMitchell, Braxton D
dc.contributor.authorFurie, Karen
dc.contributor.authorClarke, Robert
dc.contributor.authorLevi, Christopher
dc.contributor.authorSeshadri, Sudha
dc.contributor.authorGschwendtner, Andreas
dc.contributor.authorBoncoraglio, Giorgio B
dc.contributor.authorSharma, Pankaj
dc.contributor.authorBis, Joshua C
dc.contributor.authorGretarsdottir, Solveig
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRothwell, Peter M
dc.contributor.authorRosand, Jonathan
dc.contributor.authorMeschia, James F
dc.contributor.authorStefansson, Kari
dc.contributor.authorDichgans, Martin
dc.contributor.authorMarkus, Hugh S
dc.date.accessioned2018-09-20T16:26:57Z
dc.date.available2018-09-20T16:26:57Z
dc.date.issued2012-11-01
dc.identifier.citationTraylor, Matthew; Farrall, Martin; Holliday, Elizabeth G; Sudlow, Cathie; Hopewell, Jemma C; Cheng, Yu-Ching; Fornage, Myriam; Ikram, M Arfan; Malik, Rainer; Bevan, Steve; Thorsteinsdottir, Unnur; Nalls, Mike A; Longstreth, WT; Wiggins, Kerri L; Yadav, Sunaina; Parati, Eugenio A; DeStefano, Anita L; Worrall, Bradford B; Kittner, Steven J; Khan, Muhammad Saleem; Reiner, Alex P; Helgadottir, Anna; Achterberg, Sefanja; Fernandez-Cadenas, Israel; Abboud, Sherine; Schmidt, Reinhold; Walters, Matthew; Chen, Wei-Min; Ringelstein, E Bernd; O'Donnell, Martin; Ho, Weang Kee; Pera, Joanna; Lemmens, Robin; Norrving, Bo; Higgins, Peter; Benn, Marianne; Sale, Michele; Kuhlenbäumer, Gregor; Doney, Alexander S F; Vicente, Astrid M; Delavaran, Hossein; Algra, Ale; Davies, Gail; Oliveira, Sofia A; Palmer, Colin N A; Deary, Ian; Schmidt, Helena; Pandolfo, Massimo; Montaner, Joan; Carty, Cara; de Bakker, Paul I W; Kostulas, Konstantinos; Ferro, Jose M; van Zuydam, Natalie R; Valdimarsson, Einar; Nordestgaard, Børge G; Lindgren, Arne; Thijs, Vincent; Slowik, Agnieszka; Saleheen, Danish; Paré, Guillaume; Berger, Klaus; Thorleifsson, Gudmar; Hofman, Albert; Mosley, Thomas H; Mitchell, Braxton D; Furie, Karen; Clarke, Robert; Levi, Christopher; Seshadri, Sudha; Gschwendtner, Andreas; Boncoraglio, Giorgio B; Sharma, Pankaj; Bis, Joshua C; Gretarsdottir, Solveig; Psaty, Bruce M; Rothwell, Peter M; Rosand, Jonathan; Meschia, James F; Stefansson, Kari; Dichgans, Martin; Markus, Hugh S (2012). Genetic risk factors for ischaemic stroke and its subtypes (the metastroke collaboration): a meta-analysis of genome-wide association studies. The Lancet Neurology 11 (11), 951-962
dc.identifier.issn1474-4422
dc.identifier.urihttp://hdl.handle.net/10379/14194
dc.description.abstractBackground Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nudeotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2.8x10(-16)) and ZFHX3 (p=2.28x10(-8)), and for large-vessel stroke at a 9p21 locus (p=3.32x10(-5)) and HDAC9 (p=2.03x10(-12)). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5x10(-6). However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.
dc.publisherElsevier BV
dc.relation.ispartofThe Lancet Neurology
dc.subjectsequence variants
dc.subjectloci
dc.subjectpopulation
dc.subjectinfarction
dc.subjectdiseases
dc.subjectcommon
dc.subjectprkch
dc.subjectmap
dc.titleGenetic risk factors for ischaemic stroke and its subtypes (the metastroke collaboration): a meta-analysis of genome-wide association studies
dc.typeArticle
dc.identifier.doi10.1016/s1474-4422(12)70234-x
dc.local.publishedsourcehttps://doi.org/10.1016/s1474-4422(12)70234-x
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