Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies

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Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies
 
Helsinki Stroke, Study Dutch Parelsnoer Institute-Cerebrovascular Accident (CVA) Study Group; National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network; UK DNA Lacunar Stroke Study Investigators; International Stroke Genetics Consortium
(2021) The Lancet Neurology, volume 20, issue 5, pp. 351 - 361
(Article)
Abstract
BACKGROUND: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease. METHODS: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar ... read more
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Keywords: Clinical Neurology
DOI: https://doi.org/10.1016/S1474-4422(21)00031-4
ISSN: 1474-4422
Publisher: Elsevier Limited
Note: Funding Information: The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. The survey was done by NatCen and the genome-wide scan data were analysed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https://www.understandingsociety.ac.uk/ . This research made use of the UK Biobank Resource under application number 36509. Ethical approval for UK Biobank was received from the research ethics committee (REC reference 11/NW/0382). We are grateful to deCODE genetics for providing data for this analysis. We acknowledge the contribution of Giorgio Boncoraglio (Fondazione IRCCS Instituto Neurologico Carlo Besta, Milan, Italy). This work, including collection and genotyping of the UK Young Lacunar Stroke DNA Study 2 (DNA Lacunar 2), was supported by a British Heart Foundation Programme Grant (RG/16/4/32218) . The NINDS Stroke Genetics Network study was funded by the US National Institute of Neurological Disorders and Stroke, National Institutes of Health ( U01 NS069208 and R01 NS100178 ). Collection of the UK Young Lacunar Stroke DNA Study 1 (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952), with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples was supported by a Stroke Association Grant (TSA 2013/01). The principal funding for the WTCCC2 stroke study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). Collection and genotyping of the Sahlgrenska Academy Study on Ischemic Stroke were primarily supported by the Swedish Research Council (grant #2018–02543), the Swedish Heart and Lung Foundation (20190203), and the Swedish state under the agreement between the Swedish government and the county councils (the ALF agreement, ALFGBG-720081). The genetic data from Geisinger was made available through the collaboration with Regeneron Genetic Centre. The Edinburgh Mild Stroke Study (MSS2) was funded by the Wellcome Trust (WT088134/Z/09/A). MT was supported by The Barts Charity and the National Institute of Health Research (NIHR) Barts Biomedical Research Centre. RL is a senior clinical investigator of FWO Flanders. PMR and the Oxford Vascular Study are funded by the NIHR Oxford Biomedical Research Centre and the Wellcome Trust. CDA is supported by the US National Institutes of Health (R01NS103924 and K23NS086873). CML is supported by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. HSM is supported by an NIHR Senior Investigator award, and his work is supported by the Cambridge Universities NIHR Comprehensive Biomedical Research Centre. Funding Information: The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. The survey was done by NatCen and the genome-wide scan data were analysed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https://www.understandingsociety.ac.uk/. This research made use of the UK Biobank Resource under application number 36509. Ethical approval for UK Biobank was received from the research ethics committee (REC reference 11/NW/0382). We are grateful to deCODE genetics for providing data for this analysis. We acknowledge the contribution of Giorgio Boncoraglio (Fondazione IRCCS Instituto Neurologico Carlo Besta, Milan, Italy). This work, including collection and genotyping of the UK Young Lacunar Stroke DNA Study 2 (DNA Lacunar 2), was supported by a British Heart Foundation Programme Grant (RG/16/4/32218). The NINDS Stroke Genetics Network study was funded by the US National Institute of Neurological Disorders and Stroke, National Institutes of Health (U01 NS069208 and R01 NS100178). Collection of the UK Young Lacunar Stroke DNA Study 1 (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952), with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples was supported by a Stroke Association Grant (TSA 2013/01). The principal funding for the WTCCC2 stroke study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). Collection and genotyping of the Sahlgrenska Academy Study on Ischemic Stroke were primarily supported by the Swedish Research Council (grant #2018–02543), the Swedish Heart and Lung Foundation (20190203), and the Swedish state under the agreement between the Swedish government and the county councils (the ALF agreement, ALFGBG-720081). The genetic data from Geisinger was made available through the collaboration with Regeneron Genetic Centre. The Edinburgh Mild Stroke Study (MSS2) was funded by the Wellcome Trust (WT088134/Z/09/A). MT was supported by The Barts Charity and the National Institute of Health Research (NIHR) Barts Biomedical Research Centre. RL is a senior clinical investigator of FWO Flanders. PMR and the Oxford Vascular Study are funded by the NIHR Oxford Biomedical Research Centre and the Wellcome Trust. CDA is supported by the US National Institutes of Health (R01NS103924 and K23NS086873). CML is supported by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. HSM is supported by an NIHR Senior Investigator award, and his work is supported by the Cambridge Universities NIHR Comprehensive Biomedical Research Centre. Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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