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

Celine Bellenguez; Steve Bevan; Andreas Gschwendtner; Chris C. A. Spencer; Annette I. Burgess; Matti Pirinen; Caroline A. Jackson; Matthew Traylor; Amy Strange; Zhan Su; Gavin Band; Paul D. Syme; Rainer Malik; Joanna Pera; Bo Norrving; Robin Lemmens; Colin Freeman; Renata Schanz; Tom James; Deborah Poole; Lee Murphy; Helen Segal; Lynelle Cortellini; Yu-Ching Cheng; Daniel Woo; Michael A. Nalls; Bertram Mueller-Myhsok; Christa Meisinger; Udo Seedorf; Helen Ross-Adams; Steven Boonen; Dorota Wloch-Kopec; Valerie Valant; Julia Slark; Karen Furie; Hossein Delavaran; Cordelia Langford; Panos Deloukas; Sarah Edkins; Sarah Hunt; Emma Gray; Serge Dronov; Leena Peltonen; Solveig Gretarsdottir; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; Giorgio B. Boncoraglio; Eugenio A. Parati; John Attia; Elizabeth Holliday; Chris Levi; Maria-Grazia Franzosi; Anuj Goel; Anna Helgadottir; Jenefer 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; Stephen J. Sawcer; Richard C. Trembath; Ananth C. Viswanathan; Nicholas W. Wood; Bradford B. Worrall; Steven J. Kittner; Braxton D. Mitchell; Brett Kissela; James F. Meschia; Vincent Thijs; Arne Lindgren; Mary Joan Macleod; Agnieszka Slowik; Matthew Walters; Jonathan Rosand; Pankaj Sharma; Martin Farrall; Cathie L. M. Sudlow; Peter M. Rothwell; Martin Dichgans; Peter Donnelly; Hugh S. Markus; ISGC

doi:10.1038/ng.1081

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

Journal article

Peer reviewed

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

Celine Bellenguez, Steve Bevan, Andreas Gschwendtner, Chris C. A. Spencer, Annette I. Burgess, Matti Pirinen, Caroline A. Jackson, Matthew Traylor, Amy Strange, Zhan Su, …

Nature genetics, Vol.44(3), pp.328-U141

01/03/2012

DOI: https://doi.org/10.1038/ng.1081

PMCID: PMC3303115

PMID: 22306652

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 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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Title: Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Creators - without role: Celine Bellenguez - University of Oxford
Steve Bevan - University of London
Andreas Gschwendtner - Univ Munich, Univ Munchen Klinikum, Inst Stroke & Dementia Res, Munich, Germany
Chris C. A. Spencer - University of Oxford
Annette I. Burgess - University of Oxford
Matti Pirinen - University of Oxford
Caroline A. Jackson - University of Edinburgh
Matthew Traylor - University of London
Amy Strange - University of Oxford
Zhan Su - University of Oxford
Gavin Band - University of Oxford
Paul D. Syme - University of Aberdeen
Rainer Malik - Univ Munich, Univ Munchen Klinikum, Inst Stroke & Dementia Res, Munich, Germany
Joanna Pera - Jagiellonian University
Bo Norrving - Lund University
Robin Lemmens - Univ Hosp Leuven, Dept Neurol, Louvain, Belgium
Colin Freeman - University of Oxford
Renata Schanz - University of London
Tom James - University of London
Deborah Poole - University of Oxford
Lee Murphy - University of Edinburgh
Helen Segal - University of Oxford
Lynelle Cortellini - Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA
Yu-Ching Cheng - Supreme Council Of Health
Daniel Woo - University of Cincinnati
Michael A. Nalls - NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA
Bertram Mueller-Myhsok - Max
Christa Meisinger - Helmholtz Zentrum München
Udo Seedorf - University of Münster
Helen Ross-Adams - Jagiellonian University
Steven Boonen - College Station Medical Center
Dorota Wloch-Kopec - Jagiellonian University
Valerie Valant - Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA
Julia Slark - University of London
Karen Furie - Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA
Hossein Delavaran - Lund University
Cordelia Langford - Wellcome Sanger Institute
Panos Deloukas - Wellcome Sanger Institute
Sarah Edkins - Wellcome Sanger Institute
Sarah Hunt - Wellcome Sanger Institute
Emma Gray - Wellcome Sanger Institute
Serge Dronov - Wellcome Sanger Institute
Leena Peltonen - Wellcome Sanger Institute
Solveig Gretarsdottir - deCODE Genet, Reykjavik, Iceland
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
Giorgio B. Boncoraglio - Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Ist Neurol Carlo Besta, Milan, Italy
Eugenio A. Parati - Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Ist Neurol Carlo Besta, Milan, Italy
John Attia - College Station Medical Center
Elizabeth Holliday - College Station Medical Center
Chris Levi - College Station Medical Center
Maria-Grazia Franzosi - Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy
Anuj Goel - University of Oxford
Anna Helgadottir - University of Oxford
Jenefer M. Blackwell - University of Western Australia
Elvira Bramon - College Station Medical Center
Matthew A. Brown - University of Queensland
Juan P. Casas - Supreme Council Of Health
Aiden Corvin - College Station Medical Center
Audrey Duncanson - Wellcome Trust
Janusz Jankowski - Supreme Council Of Health
Christopher G. Mathew - Supreme Council Of Health
Colin N. A. Palmer - University of Dundee
Robert Plomin - Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England
Anna Rautanen - University of Oxford
Stephen J. Sawcer - University of Cambridge
Richard C. Trembath - Supreme Council Of Health
Ananth C. Viswanathan - Natl Hlth Serv NHS Fdn Trust, Moorfields Eye Hosp, Biomed Res Ctr Ophthalmol, Natl Inst Hlth Res NIHR, London, England
Nicholas W. Wood - UCL, Inst Neurol, Dept Mol Neuroscience, London, England
Bradford B. Worrall - University of Virginia
Steven J. Kittner - Supreme Council Of Health
Braxton D. Mitchell - Supreme Council Of Health
Brett Kissela - University of Cincinnati
James F. Meschia - Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA
Vincent Thijs - Univ Hosp Leuven, Dept Neurol, Louvain, Belgium
Arne Lindgren - Lund University
Mary Joan Macleod - University of Aberdeen
Agnieszka Slowik - Jagiellonian University
Matthew Walters - University of Glasgow
Jonathan Rosand - Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA
Pankaj Sharma - University of London
Martin Farrall - University of Oxford
Cathie L. M. Sudlow - University of Edinburgh
Peter M. Rothwell - University of Oxford
Martin Dichgans - Univ Munich, Univ Munchen Klinikum, Inst Stroke & Dementia Res, Munich, Germany
Peter Donnelly - University of Oxford
Hugh S. Markus - University of London
ISGC
Publication Details: Nature genetics, Vol.44(3), pp.328-U141
Publisher: Springer Nature
Number of pages: 8
Grant note: 068545/Z/02; 085475/B/08/Z; 085475/Z/08/Z; WT084724MA; WTCCC2 / Wellcome Trust NF-SI-0507-10379; PDA/02/06/016 / National Institute for Health Research; National Institutes of Health Research (NIHR) G0901310; G1001799; G0000934 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0000934; G9817803B; G0901310; G1001799 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9938402008331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article