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Neurology
Protocol
Towards the genetic basis of cerebral venous thrombosis—the BEAST Consortium: a study protocol
  1. Ioana Cotlarciuc1,
  2. Thomas Marjot2,
  3. Muhammad S Khan3,
  4. Sini Hiltunen4,
  5. Elena Haapaniemi4,
  6. Tiina M Metso4,
  7. Jukka Putaala4,
  8. Susanna M Zuurbier5,
  9. Matthijs C Brouwer5,
  10. Serena M Passamonti6,
  11. Paolo Bucciarelli6,
  12. Emanuela Pappalardo6,
  13. Tasmin Patel1,
  14. Paolo Costa7,
  15. Marina Colombi8,
  16. Patrícia Canhão9,
  17. Aleksander Tkach10,
  18. Rosa Santacroce11,
  19. Maurizio Margaglione11,
  20. Giovanni Favuzzi12,
  21. Elvira Grandone12,
  22. Donatella Colaizzo12,
  23. Kostas Spengos13,
  24. Antonio Arauz14,
  25. Amanda Hodge15,
  26. Reina Ditta15,
  27. Stephanie Debette16,
  28. Marialuisa Zedde17,
  29. Guillaume Pare15,
  30. José M Ferro9,
  31. Vincent Thijs18,
  32. Alessandro Pezzini7,
  33. Jennifer J Majersik10,
  34. Ida Martinelli6,
  35. Jonathan M Coutinho5,
  36. Turgut Tatlisumak4,19,20,
  37. Pankaj Sharma1
  38. on behalf of the ISGC (International Stroke Genetics Consortium) and BEAST investigators
  1. 1Institute of Cardiovascular Research Royal Holloway, University of London (ICR2UL), London, UK
  2. 2Department of Gastroenterology and Hepatology, University of Oxford, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK
  3. 3Department of Restorative Neuroscience, Imperial College London, London, UK
  4. 4Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
  5. 5Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  6. 6Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  7. 7Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy
  8. 8Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy
  9. 9Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal
  10. 10Department of Neurology, University of Utah, Salt Lake City, Utah, USA
  11. 11Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
  12. 12Atherosclerosis and Thrombosis Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
  13. 13Department of Neurology, University of Athens School of Medicine, Eginition Hospital, Athens, Greece
  14. 14Stroke Clinic, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico
  15. 15Department of Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
  16. 16Department of Neurology, Bordeaux University Hospital, Bordeaux University, Bordeaux, France
  17. 17Neurology Unit, Stroke Unit, Arcispedale Santa Maria Nuova—IRCCS, Reggio Emilia, Italy
  18. 18Department of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia
  19. 19Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  20. 20Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
  1. Correspondence to Dr Ioana Cotlarciuc; ioana.cotlarciuc{at}rhul.ac.uk

Abstract

Introduction Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated.

Methods and analysis To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case–control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease.

Ethics and dissemination BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders.

  • cerebral venous thrombosis
  • ischemic stroke

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2016-012351

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    Footnotes

    • IC and TM contributed equally to this work

    • Contributors IC was involved in study design, recruitment, contributed to developing the final protocol and drafted the manuscript. TM was involved in study design, recruitment, contributed to developing the final protocol and revising the manuscript. MSK, TP, AH and RD were involved in laboratory analysis and management of samples. SH, EH, TMM, JP, SMZ, MCB, SMP, PB, EP, PC, MC, PC, AT, RS, GF and DC were involved in recruitment and laboratory analysis. MM, EG, MZ, KS, AA, SD, GP, JMF, VT, AP, JJM, IM, JMC and TT are senior investigators who contributed with recruitment and sample collection. PS conceived the idea and is the principal investigator of BEAST who developed the final protocol and drafted the manuscript. All authors contributed intellectually to the protocol and draft versions of the manuscript and approved the final manuscript.

    • Funding BEAST has received financial support from the Dowager Countess Eleanor Peel Trust and from the Stroke Association.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval UK Research Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.