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

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Acknowledgements

We thank S. Bertrand, J. Bryant, S.L. Clark, J.S. Conquer, T. Dibling, J.C. Eldred, S. Gamble, C. Hind, M.L. Perez, C.R. Stribling, S. Taylor and A. Wilk of the Wellcome Trust Sanger Institute's Sample and Genotyping Facilities for technical assistance. We acknowledge use of the British 1958 Birth Cohort DNA collection, which is funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02), and of the UK National Blood Service controls funded by the Wellcome Trust. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank the following individuals who contributed to collection, phenotyping, sample processing and data management for the different cohorts: A. Burgess, A. Syed and N. Paul (Oxford Vascular Study); M. Dennis, P. Sandercock, C. Warlow, S. Hart, S. Keir, J. Wardlaw, A. Farrall, G. Potter, A. Hutchison and M. McDowall (Edinburgh Stroke Study); A. Pasdar and H. Clinkscale (Aberdeen); P. Higgins (Glasgow); T.G. Brott, R.D. Brown, S. Silliman, M. Frankel, D. Case, S. Rich, J. Hardy, A. Singleton (ISGS); M.J. Sparks, K. Ryan, J. Cole, M. Wozniak, B. Stern, R. Wityk, C. Johnson and D. Buchholz (GEOS); and J. Maguire, S. Koblar, J. Golledge, J. Surm, G. Hankey, J. Jannes, M. Lewis, R. Scott, L. Lincz; P. Moscato and R. Baker (Australian Stroke Genetics Collaborative membership). The principal funding for this study was provided by the Wellcome Trust as part of the WTCCC2 project (085475/B/08/Z, 085475/Z/08/Z and WT084724MA). For details of other funding support, see the Supplementary Note.

Author information

Author notes

  1. Céline Bellenguez and Steve Bevan: These authors contributed equally to this work.
  2. Peter Donnelly and Hugh S Markus: These authors jointly directed this work.
  3. Leena Peltonen: Deceased.

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Céline Bellenguez, Chris C A Spencer, Matti Pirinen, Amy Strange, Zhan Su, Gavin Band, Colin Freeman, Anuj Goel, Anna Helgadottir, Anna Rautanen, Martin Farrall & Peter Donnelly
  2. Stroke and Dementia Research Group, St. George's University of London, London, UK
    Steve Bevan, Matthew Traylor, Tom James & Hugh S Markus
  3. Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany
    Andreas Gschwendtner, Rainer Malik & Martin Dichgans
  4. Nuffield Department of Clinical Neuroscience, Stroke Prevention Research Unit, University of Oxford, Oxford, UK
    Annette I Burgess, Deborah Poole, Helen Segal & Peter M Rothwell
  5. Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    Caroline A Jackson & Cathie L M Sudlow
  6. Division of Applied Medicine, University of Aberdeen, Aberdeen, UK
    Paul D Syme & Mary Joan Macleod
  7. Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
    Joanna Pera, Helen Ross-Adams, Dorota Wloch-Kopec & Agnieszka Slowik
  8. Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden
    Bo Norrving, Hossein Delavaran & Arne Lindgren
  9. Department of Neurology, Skåne University Hospital, Lund, Sweden
    Bo Norrving, Hossein Delavaran & Arne Lindgren
  10. Department of Neurology, University Hospitals Leuven, Leuven, Belgium
    Robin Lemmens & Vincent Thijs
  11. Vesalius Research Center, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
    Robin Lemmens & Vincent Thijs
  12. Imperial College Cerebrovascular Research Unit (ICCRU), Imperial College London, London, UK
    Renata Schanz, Julia Slark & Pankaj Sharma
  13. Wellcome Trust Clinical Research Facility Genetics Core Laboratory, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Lee Murphy
  14. Department of Neurology, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Lynelle Cortellini, Valerie Valant, Karen Furie & Jonathan Rosand
  15. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
    Lynelle Cortellini, Valerie Valant & Jonathan Rosand
  16. Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Yu-Ching Cheng & Braxton D Mitchell
  17. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Yu-Ching Cheng & Braxton D Mitchell
  18. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Daniel Woo & Brett Kissela
  19. Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA
    Michael A Nalls
  20. Max Planck Institute of Psychiatry, Munich, Germany
    Bertram Müller-Myhsok
  21. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany
    Christa Meisinger
  22. Leibniz–Institut für Arterioskleroseforschung, Universität Münster, Münster, Germany
    Udo Seedorf
  23. Division of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium
    Steven Boonen
  24. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
    Cordelia Langford, Panos Deloukas, Sarah Edkins, Sarah Hunt, Emma Gray, Serge Dronov & Leena Peltonen
  25. deCODE Genetics, Reykjavik, Iceland
    Solveig Gretarsdottir, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Kari Stefansson & Anna Helgadottir
  26. University of Iceland, Faculty of Medicine, Reykjavik, Iceland
    Unnur Thorsteinsdottir & Kari Stefansson
  27. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan, Italy
    Giorgio B Boncoraglio & Eugenio A Parati
  28. Centre for Brain and Mental Health Research, University of Newcastle, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
    John Attia, Elizabeth Holliday & Chris Levi
  29. Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Maria-Grazia Franzosi
  30. Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
    Anuj Goel, Anna Helgadottir & Martin Farrall
  31. Centre for Child Health Research, University of Western Australia, West Perth, Western Australia, Australia
    Jenefer M Blackwell
  32. Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Cambridge, UK
    Jenefer M Blackwell
  33. Division of Psychological Medicine and Psychiatry, Biomedical Research Centre for Mental Health, Institute of Psychiatry, King's College London, London, UK
    Elvira Bramon
  34. The University of Queensland Diamantina Institute, Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia
    Matthew A Brown
  35. Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
    Juan P Casas
  36. Department of Epidemiology and Public Health, University College London, London, UK
    Juan P Casas
  37. Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
    Aiden Corvin
  38. Molecular and Physiological Sciences, The Wellcome Trust, London, London, UK
    Audrey Duncanson
  39. Centre for Gastroenterology, Barts and the London School of Medicine and Dentistry, London, UK
    Janusz Jankowski
  40. Division of Clinical Pharmacology, University of Oxford, Oxford, UK
    Janusz Jankowski
  41. Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK
    Christopher G Mathew & Richard C Trembath
  42. Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK
    Colin N A Palmer
  43. Social, Genetic and Developmental Psychiatry Centre, King's College London Institute of Psychiatry, Denmark Hill, London, UK.,
    Robert Plomin
  44. University of Cambridge Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK
    Stephen J Sawcer
  45. National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and University College London Institute of Ophthalmology, London, UK
    Ananth C Viswanathan
  46. Department of Molecular Neuroscience, Institute of Neurology, Queen Square, University College London, London, UK
    Nicholas W Wood
  47. Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
    Bradford B Worrall
  48. Department of Public Health Science, University of Virginia School of Medicine, Charlottesville, Virginia, USA
    Bradford B Worrall
  49. Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Steven J Kittner
  50. Baltimore Geriatric Research, Education, and Clinical Center, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
    Steven J Kittner
  51. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
    James F Meschia
  52. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
    Matthew Walters
  53. Department of Statistics, University of Oxford, Oxford, UK
    Peter Donnelly

Authors

  1. Céline Bellenguez
  2. Steve Bevan
  3. Andreas Gschwendtner
  4. Chris C A Spencer
  5. Annette I Burgess
  6. Matti Pirinen
  7. Caroline A Jackson
  8. Matthew Traylor
  9. Amy Strange
  10. Zhan Su
  11. Gavin Band
  12. Paul D Syme
  13. Rainer Malik
  14. Joanna Pera
  15. Bo Norrving
  16. Robin Lemmens
  17. Colin Freeman
  18. Renata Schanz
  19. Tom James
  20. Deborah Poole
  21. Lee Murphy
  22. Helen Segal
  23. Lynelle Cortellini
  24. Yu-Ching Cheng
  25. Daniel Woo
  26. Michael A Nalls
  27. Bertram Müller-Myhsok
  28. Christa Meisinger
  29. Udo Seedorf
  30. Helen Ross-Adams
  31. Steven Boonen
  32. Dorota Wloch-Kopec
  33. Valerie Valant
  34. Julia Slark
  35. Karen Furie
  36. Hossein Delavaran
  37. Cordelia Langford
  38. Panos Deloukas
  39. Sarah Edkins
  40. Sarah Hunt
  41. Emma Gray
  42. Serge Dronov
  43. Leena Peltonen
  44. Solveig Gretarsdottir
  45. Gudmar Thorleifsson
  46. Unnur Thorsteinsdottir
  47. Kari Stefansson
  48. Giorgio B Boncoraglio
  49. Eugenio A Parati
  50. John Attia
  51. Elizabeth Holliday
  52. Chris Levi
  53. Maria-Grazia Franzosi
  54. Anuj Goel
  55. Anna Helgadottir
  56. Jenefer M Blackwell
  57. Elvira Bramon
  58. Matthew A Brown
  59. Juan P Casas
  60. Aiden Corvin
  61. Audrey Duncanson
  62. Janusz Jankowski
  63. Christopher G Mathew
  64. Colin N A Palmer
  65. Robert Plomin
  66. Anna Rautanen
  67. Stephen J Sawcer
  68. Richard C Trembath
  69. Ananth C Viswanathan
  70. Nicholas W Wood
  71. Bradford B Worrall
  72. Steven J Kittner
  73. Braxton D Mitchell
  74. Brett Kissela
  75. James F Meschia
  76. Vincent Thijs
  77. Arne Lindgren
  78. Mary Joan Macleod
  79. Agnieszka Slowik
  80. Matthew Walters
  81. Jonathan Rosand
  82. Pankaj Sharma
  83. Martin Farrall
  84. Cathie L M Sudlow
  85. Peter M Rothwell
  86. Martin Dichgans
  87. Peter Donnelly
  88. Hugh S Markus

Consortia

The International Stroke Genetics Consortium (ISGC)

the Wellcome Trust Case Control Consortium 2 (WTCCC2)

Contributions

S. Bevan, C.C.A.S., P.S., M.F., C.L.M.S., P.M.R., M.D., P. Donnelly and H.S.M. designed the experiment. S. Bevan, A.G., A.I.B., C.A.J., T.J., D.P., L.M., H.S., C.L.M.S., P.M.R., M.D. and H.S.M. were responsible for collecting and phenotyping discovery samples. Replication sample or replication data were provided by P.D.S., J.P., B.N., R.L., R.S., L.C., Y.-C.C., D.W., M.A.N., U.S., H.R.-A., S. Boonen, D.W.-K., V.V., J.S., K.F., H.D., S.G., G.T., U.T., K.S., G.B.B., E.A.P., J.A., E.H., C.L., M.-G.F., A.H., B.B.W., S.J.K., B.D.M., B.K., J.F.M., V.T., A.L., M.J.M., A.S., M.W., J.R. and P.S. Genotyping, quality control and informatics were conducted by C.B., S. Bevan, C.C.A.S., M.P., M.T., A.S., Z.S., G.B., C.F., R.M., B.M.-M., C.M., C.L., S.E., S.H., E.G., S.D., A.G., M.F., P. Donnelly and H.S.M. Genetic and statistical analysis was performed by C.B., S.B., C.C.A.S., M.P., A.S., Z.S., G.B., C.F., M.T., R.M., A.H., M.F. and P. Donnelly. The WTCCC2 management committee (P. Donnelly (Chair), L.P. (Deputy Chair), J.M.B., E.B., M.A.B., J.P.C., A.C., P. Deloukas, A.D., J.J., H.S.M., C.G.M., C.N.A.P., R.P., A.R., S.J.S., R.C.T., A.C.V. and N.W.W.) monitored the execution of the study. C.B., S. Bevan, C.C.A.S., M.P., M.F., P. Donnelly and H.S.M. contributed to writing the first draft of the manuscript. All authors reviewed and commented on the final manuscript.

Corresponding authors

Correspondence toPeter Donnelly or Hugh S Markus.

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The authors declare no competing financial interests.

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A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

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The International Stroke Genetics Consortium (ISGC)., the Wellcome Trust Case Control Consortium 2 (WTCCC2)., Bellenguez, C. et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke.Nat Genet 44, 328–333 (2012). https://doi.org/10.1038/ng.1081

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