DOI: 10.1038/ng.1081

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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Céline Bellenguez,Steve Bevan,Andreas Gschwendtner,Spencer Cca.,A I Burgess,Matti Pirinen,Caroline Jackson,Matthew Traylor,Amy Strange,Zhan Su,Paul D. Syme,Rainer Malik,Joanna Pera,Bo Niu,Robin Lemmens,Colin Freeman,Renata Schanz,Thomas N. James,D L Poole,Lee Murphy,Helen Segal,Lynelle Cortellini,Yuehua Cheng,Daniel Woo,Michael A. Nalls,Bertram Müller‐Myhsok,Christa Meisinger,Udo Seedorf,Helen Ross-Adams,Steven Boonen,Dorota Włoch-Kopeć,Valerie Valant,Julia Slark,Karen L. Furie,Hossein Delavaran,Cordelia Langford,Panos Deloukas,Sarah Edkins,Sarah Hunt,Emma Gray,Serge Dronov,Leena Peltonen,Sólveig Grétarsdóttir,Guðmar Þorleifsson,Unnur Þorsteinsdóttir,Kāri Stefánsson,Giorgio B. Boncoraglio,Eugenio Parati,John Attia,Elizabeth G. Holliday,Christopher Levi,Franzosi M-G.,Anuj Goel,Anna Helgadóttir,J. M. Blackwell,Elvira Bramon,Matthew A. Brown,Juan P. Casas,Aiden Corvin,Audrey Duncanson,Janusz Jankowski,Christopher G. Mathew,Colin N.A. Palmer,Robert Plomin,Anna Rautanen,S. J. Sawcer,Richard C. Trembath,Ananth C. Viswanathan,Nicholas W. Wood,Bradford B. Worrall,Steven J. Kittner,Braxton D. Mitchell,Brett M. Kissela,James F. Meschia,Vincent Thijs,Arne Lindgren,Mary Joan MacLeod,Agnieszka Słowik,James Walters,Jonathan Rosand,Pankaj Sharma,Martin Farrall,Cathie Sudlow,Peter M. Rothwell,Martin Dichgans,Peter Donnelly,Hugh S. Markus

Genome-wide association study

Biology

Odds ratio

2012

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

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“Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke” is a paper by Céline Bellenguez Steve Bevan Andreas Gschwendtner Spencer Cca. A I Burgess Matti Pirinen Caroline Jackson Matthew Traylor Amy Strange Zhan Su Paul D. Syme Rainer Malik Joanna Pera Bo Niu Robin Lemmens Colin Freeman Renata Schanz Thomas N. James D L Poole Lee Murphy Helen Segal Lynelle Cortellini Yuehua Cheng Daniel Woo Michael A. Nalls Bertram Müller‐Myhsok Christa Meisinger Udo Seedorf Helen Ross-Adams Steven Boonen Dorota Włoch-Kopeć Valerie Valant Julia Slark Karen L. Furie Hossein Delavaran Cordelia Langford Panos Deloukas Sarah Edkins Sarah Hunt Emma Gray Serge Dronov Leena Peltonen Sólveig Grétarsdóttir Guðmar Þorleifsson Unnur Þorsteinsdóttir Kāri Stefánsson Giorgio B. Boncoraglio Eugenio Parati John Attia Elizabeth G. Holliday Christopher Levi Franzosi M-G. Anuj Goel Anna Helgadóttir J. M. Blackwell Elvira Bramon Matthew A. Brown Juan P. Casas Aiden Corvin Audrey Duncanson Janusz Jankowski Christopher G. Mathew Colin N.A. Palmer Robert Plomin Anna Rautanen S. J. Sawcer Richard C. Trembath Ananth C. Viswanathan Nicholas W. Wood Bradford B. Worrall Steven J. Kittner Braxton D. Mitchell Brett M. Kissela James F. Meschia Vincent Thijs Arne Lindgren Mary Joan MacLeod Agnieszka Słowik James Walters Jonathan Rosand Pankaj Sharma Martin Farrall Cathie Sudlow Peter M. Rothwell Martin Dichgans Peter Donnelly Hugh S. Markus published in 2012. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.