Genome-wide association analysis of young onset stroke identifies a locus on chromosome 10q25 near HABP2
Identifieur interne : 001E37 ( Main/Curation ); précédent : 001E36; suivant : 001E38Genome-wide association analysis of young onset stroke identifies a locus on chromosome 10q25 near HABP2
Auteurs : Yu-Ching Cheng [États-Unis] ; Tara M. Stanne [Suède] ; Anne-Katrin Giese [Allemagne] ; Weang Kee Ho [Malaisie] ; Matthew Traylor [Royaume-Uni] ; Philippe Amouyel [France] ; Elizabeth G. Holliday [Australie] ; Rainer Malik [Allemagne] ; Huichun Xu [États-Unis] ; Steven J. Kittner [États-Unis] ; John W. Cole [États-Unis] ; Jeffrey R. O Onnell [États-Unis] ; John Danesh [Royaume-Uni] ; Asif Rasheed [Pakistan] ; Wei Zhao [États-Unis] ; Stefan Engelter [Suisse] ; Caspar Grond-Ginsbach [Allemagne] ; Yoichiro Kamatani [France, Japon] ; Mark Lathrop [France, Canada] ; Didier Leys [France] ; Vincent Thijs [Belgique] ; Tiina M. Metso [Finlande] ; Turgut Tatlisumak [Finlande] ; Alessandro Pezzini [Italie] ; Eugenio A. Parati [Italie] ; Bo Norrving [Suède] ; Steve Bevan [Royaume-Uni] ; Peter M. Rothwell [Royaume-Uni] ; Cathie Sudlow [Royaume-Uni] ; Agnieszka Slowik [Pologne] ; Arne Lindgren [Suède] ; Matthew R. Walters [Royaume-Uni] ; Jim Jannes [Australie] ; Jess Shen [Canada] ; David Crosslin [États-Unis] ; Kimberly Doheny [États-Unis] ; Cathy C. Laurie [États-Unis] ; Sandip M. Kanse [Norvège] ; Joshua C. Bis [États-Unis] ; Myriam Fornage [États-Unis] ; Thomas H. Mosley [États-Unis] ; Jemma C. Hopewell [Royaume-Uni] ; Konstantin Strauch [Allemagne] ; Martina Müller-Nurasyid [Allemagne] ; Christian Gieger [Allemagne] ; Melanie Waldenberger [Allemagne] ; Annette Peters [Allemagne] ; Christine Meisinger [Allemagne] ; M. Arfan Ikram [Pays-Bas] ; Wt Longstreth [États-Unis] ; James F. Meschia [États-Unis] ; Sudha Seshadri [États-Unis] ; Pankaj Sharma [Royaume-Uni] ; Bradford Worrall [États-Unis] ; Christina Jern [Suède] ; Christopher Levi [Australie] ; Martin Dichgans [Allemagne] ; Giorgio B. Boncoraglio [Italie] ; Hugh S. Markus [Royaume-Uni] ; Stephanie Debette [Royaume-Uni, France] ; Arndt Rolfs [Allemagne] ; Danish Saleheen [Royaume-Uni, Pakistan, États-Unis] ; Braxton D. Mitchell [États-Unis]Source :
- Stroke; a journal of cerebral circulation [ 0039-2499 ] ; 2016.
Descripteurs français
- KwdFr :
- ADN intergénique (génétique), Accident vasculaire cérébral (génétique), Accident vasculaire cérébral (étiologie), Adulte, Adulte d'âge moyen, Chromosomes humains de la paire 10, Encéphalopathie ischémique (), Encéphalopathie ischémique (génétique), Femelle, Humains, Mâle, Odds ratio, Polymorphisme de nucléotide simple, Population d'origine africaine (génétique), Population d'origine asiatique (génétique), Population d'origine européenne (génétique), Prédisposition génétique à une maladie, Serine endopeptidases (génétique), Serine endopeptidases (métabolisme), Simulation numérique, Sujet âgé, Âge de début, Étude d'association pangénomique.
- MESH :
- génétique : ADN intergénique, Accident vasculaire cérébral, Encéphalopathie ischémique, Population d'origine africaine, Population d'origine asiatique, Population d'origine européenne, Serine endopeptidases.
- métabolisme : Serine endopeptidases.
- étiologie : Accident vasculaire cérébral.
- Adulte, Adulte d'âge moyen, Chromosomes humains de la paire 10, Encéphalopathie ischémique, Femelle, Humains, Mâle, Odds ratio, Polymorphisme de nucléotide simple, Prédisposition génétique à une maladie, Simulation numérique, Sujet âgé, Âge de début, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Adult, African Continental Ancestry Group (genetics), Age of Onset, Aged, Asian Continental Ancestry Group (genetics), Brain Ischemia (complications), Brain Ischemia (genetics), Chromosomes, Human, Pair 10, Computer Simulation, DNA, Intergenic (genetics), European Continental Ancestry Group (genetics), Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Serine Endopeptidases (genetics), Serine Endopeptidases (metabolism), Stroke (etiology), Stroke (genetics).
- MESH :
- chemical , genetics : DNA, Intergenic, Serine Endopeptidases.
- complications : Brain Ischemia.
- etiology : Stroke.
- genetics : African Continental Ancestry Group, Asian Continental Ancestry Group, Brain Ischemia, European Continental Ancestry Group, Stroke.
- chemical , metabolism : Serine Endopeptidases.
- Adult, Age of Onset, Aged, Chromosomes, Human, Pair 10, Computer Simulation, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide.
Abstract
Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a two-stage meta-analysis of genome-wide association studies (GWAS), focusing on stroke cases with an age of onset < 60 years old.
The Discovery stage of our GWAS included 4,505 cases and 21,968 controls of European, South-Asian and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10−6 and performed
One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the Discovery and Follow-up Stages (rs11196288, OR=1.41, P=9.5×10−9). The associated locus is in an intergenic region between
Url:
DOI: 10.1161/STROKEAHA.115.011328
PubMed: 26732560
PubMed Central: 4729659
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PMC:4729659Le document en format XML
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<author><name sortKey="Thijs, Vincent" sort="Thijs, Vincent" uniqKey="Thijs V" first="Vincent" last="Thijs">Vincent Thijs</name>
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<author><name sortKey="Pezzini, Alessandro" sort="Pezzini, Alessandro" uniqKey="Pezzini A" first="Alessandro" last="Pezzini">Alessandro Pezzini</name>
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<author><name sortKey="Parati, Eugenio A" sort="Parati, Eugenio A" uniqKey="Parati E" first="Eugenio A." last="Parati">Eugenio A. Parati</name>
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<author><name sortKey="Bevan, Steve" sort="Bevan, Steve" uniqKey="Bevan S" first="Steve" last="Bevan">Steve Bevan</name>
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<author><name sortKey="Sudlow, Cathie" sort="Sudlow, Cathie" uniqKey="Sudlow C" first="Cathie" last="Sudlow">Cathie Sudlow</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Edinburgh, Edinburgh</wicri:regionArea>
<placeName><settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
</affiliation>
</author>
<author><name sortKey="Slowik, Agnieszka" sort="Slowik, Agnieszka" uniqKey="Slowik A" first="Agnieszka" last="Slowik">Agnieszka Slowik</name>
<affiliation wicri:level="1"><nlm:aff id="A29">Jagiellonian University Medical College, Krakow, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>Jagiellonian University Medical College, Krakow</wicri:regionArea>
<wicri:noRegion>Krakow</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lindgren, Arne" sort="Lindgren, Arne" uniqKey="Lindgren A" first="Arne" last="Lindgren">Arne Lindgren</name>
<affiliation wicri:level="1"><nlm:aff id="A30">Lund University, Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Lund University, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A31">Skåne University Hospital, Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Skåne University Hospital, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Walters, Matthew R" sort="Walters, Matthew R" uniqKey="Walters M" first="Matthew R" last="Walters">Matthew R. Walters</name>
<affiliation wicri:level="4"><nlm:aff id="A32">University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName><settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jannes, Jim" sort="Jannes, Jim" uniqKey="Jannes J" first="Jim" last="Jannes">Jim Jannes</name>
<affiliation wicri:level="1"><nlm:aff id="A33">University of Adelaide, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>University of Adelaide</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Shen, Jess" sort="Shen, Jess" uniqKey="Shen J" first="Jess" last="Shen">Jess Shen</name>
<affiliation wicri:level="2"><nlm:aff id="A34">Mount Sinai Hospital, Toronto, Ontario</nlm:aff>
<country>Canada</country>
<placeName><region type="province">Ontario</region>
</placeName>
<wicri:cityArea>Mount Sinai Hospital, Toronto</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Crosslin, David" sort="Crosslin, David" uniqKey="Crosslin D" first="David" last="Crosslin">David Crosslin</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Doheny, Kimberly" sort="Doheny, Kimberly" uniqKey="Doheny K" first="Kimberly" last="Doheny">Kimberly Doheny</name>
<affiliation wicri:level="2"><nlm:aff id="A36">Johns Hopkins University School of Medicine, Baltimore, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Laurie, Cathy C" sort="Laurie, Cathy C" uniqKey="Laurie C" first="Cathy C." last="Laurie">Cathy C. Laurie</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kanse, Sandip M" sort="Kanse, Sandip M" uniqKey="Kanse S" first="Sandip M." last="Kanse">Sandip M. Kanse</name>
<affiliation wicri:level="3"><nlm:aff id="A37">University of Oslo, Oslo, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>University of Oslo, Oslo</wicri:regionArea>
<placeName><settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<affiliation wicri:level="2"><nlm:aff id="A38">The University of Texas Health Science Center at Houston, Houston, Texas</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas Health Science Center at Houston, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H." last="Mosley">Thomas H. Mosley</name>
<affiliation wicri:level="2"><nlm:aff id="A39">University of Mississippi Medical Center, Jackson, MS</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État du Mississippi</region>
</placeName>
<wicri:cityArea>University of Mississippi Medical Center, Jackson</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hopewell, Jemma C" sort="Hopewell, Jemma C" uniqKey="Hopewell J" first="Jemma C." last="Hopewell">Jemma C. Hopewell</name>
<affiliation wicri:level="4"><nlm:aff id="A40">University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
</author>
<author><name sortKey="Strauch, Konstantin" sort="Strauch, Konstantin" uniqKey="Strauch K" first="Konstantin" last="Strauch">Konstantin Strauch</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A42">Partner site Munich Heart Alliance, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner site Munich Heart Alliance, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A50">University Hospital Grosshadern, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Hospital Grosshadern, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Waldenberger, Melanie" sort="Waldenberger, Melanie" uniqKey="Waldenberger M" first="Melanie" last="Waldenberger">Melanie Waldenberger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A42">Partner site Munich Heart Alliance, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner site Munich Heart Alliance, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meisinger, Christine" sort="Meisinger, Christine" uniqKey="Meisinger C" first="Christine" last="Meisinger">Christine Meisinger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M. Arfan" last="Ikram">M. Arfan Ikram</name>
<affiliation wicri:level="1"><nlm:aff id="A43">Erasmus University Medical Center Rotterdam, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Erasmus University Medical Center Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Longstreth, Wt" sort="Longstreth, Wt" uniqKey="Longstreth W" first="Wt" last="Longstreth">Wt Longstreth</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Meschia, James F" sort="Meschia, James F" uniqKey="Meschia J" first="James F." last="Meschia">James F. Meschia</name>
<affiliation wicri:level="2"><nlm:aff id="A44">Mayo Clinic, Florida</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Floride</region>
</placeName>
<wicri:cityArea>Mayo Clinic</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation wicri:level="2"><nlm:aff id="A45">Boston University School of Medicine, Boston, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Boston University School of Medicine, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sharma, Pankaj" sort="Sharma, Pankaj" uniqKey="Sharma P" first="Pankaj" last="Sharma">Pankaj Sharma</name>
<affiliation wicri:level="4"><nlm:aff id="A46">Royal Holloway, University of London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Holloway, University of London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">Université de Londres</orgName>
</affiliation>
</author>
<author><name sortKey="Worrall, Bradford" sort="Worrall, Bradford" uniqKey="Worrall B" first="Bradford" last="Worrall">Bradford Worrall</name>
<affiliation wicri:level="2"><nlm:aff id="A47">University of Virginia, Charlottesville, Virginia</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
<wicri:cityArea>University of Virginia, Charlottesville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jern, Christina" sort="Jern, Christina" uniqKey="Jern C" first="Christina" last="Jern">Christina Jern</name>
<affiliation wicri:level="1"><nlm:aff id="A3">The University of Gothenburg, Gothenburg, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>The University of Gothenburg, Gothenburg</wicri:regionArea>
<wicri:noRegion>Gothenburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Levi, Christopher" sort="Levi, Christopher" uniqKey="Levi C" first="Christopher" last="Levi">Christopher Levi</name>
<affiliation wicri:level="1"><nlm:aff id="A48">John Hunter Hospital, Newcastle, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>John Hunter Hospital, Newcastle</wicri:regionArea>
<wicri:noRegion>Newcastle</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dichgans, Martin" sort="Dichgans, Martin" uniqKey="Dichgans M" first="Martin" last="Dichgans">Martin Dichgans</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
</author>
<author><name sortKey="Boncoraglio, Giorgio B" sort="Boncoraglio, Giorgio B" uniqKey="Boncoraglio G" first="Giorgio B." last="Boncoraglio">Giorgio B. Boncoraglio</name>
<affiliation wicri:level="3"><nlm:aff id="A25">Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan</wicri:regionArea>
<placeName><settlement type="city">Milan</settlement>
<region nuts="2">Lombardie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Markus, Hugh S" sort="Markus, Hugh S" uniqKey="Markus H" first="Hugh S." last="Markus">Hugh S. Markus</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stephanie" last="Debette">Stephanie Debette</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A19">Lille University Hospital, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lille University Hospital</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A49">University Hospital of Bordeaux, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Hospital of Bordeaux</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rolfs, Arndt" sort="Rolfs, Arndt" uniqKey="Rolfs A" first="Arndt" last="Rolfs">Arndt Rolfs</name>
<affiliation wicri:level="1"><nlm:aff id="A4">University of Rostock, Rostock, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Rostock, Rostock</wicri:regionArea>
<wicri:noRegion>Rostock</wicri:noRegion>
<wicri:noRegion>Rostock</wicri:noRegion>
<wicri:noRegion>Rostock</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A11">Center for Non-communicable Diseases, Karachi, Pakistan</nlm:aff>
<country xml:lang="fr">Pakistan</country>
<wicri:regionArea>Center for Non-communicable Diseases, Karachi</wicri:regionArea>
<wicri:noRegion>Karachi</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A12">University of Pennsylvania, US</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Veterans Affairs Maryland Health Care System, Baltimore, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Veterans Affairs Maryland Health Care System, Baltimore</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">University of Maryland School of Medicine, Baltimore, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>University of Maryland School of Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
</titleStmt>
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<idno type="pmid">26732560</idno>
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<idno type="doi">10.1161/STROKEAHA.115.011328</idno>
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<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Veterans Affairs Maryland Health Care System, Baltimore</wicri:cityArea>
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<affiliation wicri:level="2"><nlm:aff id="A2">University of Maryland School of Medicine, Baltimore, Maryland</nlm:aff>
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<author><name sortKey="Cole, John W" sort="Cole, John W" uniqKey="Cole J" first="John W." last="Cole">John W. Cole</name>
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<placeName><region type="state">Maryland</region>
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<wicri:cityArea>Veterans Affairs Maryland Health Care System, Baltimore</wicri:cityArea>
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<affiliation wicri:level="2"><nlm:aff id="A2">University of Maryland School of Medicine, Baltimore, Maryland</nlm:aff>
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<wicri:regionArea>Wellcome Trust Sanger Institute, Cambridge</wicri:regionArea>
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<author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name>
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<wicri:regionArea>University of Pennsylvania</wicri:regionArea>
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</author>
<author><name sortKey="Engelter, Stefan" sort="Engelter, Stefan" uniqKey="Engelter S" first="Stefan" last="Engelter">Stefan Engelter</name>
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<wicri:regionArea>Basel University Hospital</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grond Ginsbach, Caspar" sort="Grond Ginsbach, Caspar" uniqKey="Grond Ginsbach C" first="Caspar" last="Grond-Ginsbach">Caspar Grond-Ginsbach</name>
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<wicri:regionArea>Heidelberg University Hospital</wicri:regionArea>
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</author>
<author><name sortKey="Kamatani, Yoichiro" sort="Kamatani, Yoichiro" uniqKey="Kamatani Y" first="Yoichiro" last="Kamatani">Yoichiro Kamatani</name>
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<affiliation wicri:level="1"><nlm:aff id="A16">RIKEN Center for Integrative Medical Sciences, Yokohama, Japan</nlm:aff>
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<wicri:regionArea>Genome Quebec, McGill University, Montreal</wicri:regionArea>
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<wicri:regionArea>Lille University Hospital</wicri:regionArea>
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<author><name sortKey="Thijs, Vincent" sort="Thijs, Vincent" uniqKey="Thijs V" first="Vincent" last="Thijs">Vincent Thijs</name>
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<affiliation wicri:level="1"><nlm:aff id="A21">Vesalius Research Center, VIB, B-3000 Leuven, Belgium</nlm:aff>
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<affiliation wicri:level="1"><nlm:aff id="A22">University Hospitals Leuven, B-3000 Leuven, Belgium</nlm:aff>
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<author><name sortKey="Metso, Tiina M" sort="Metso, Tiina M" uniqKey="Metso T" first="Tiina M." last="Metso">Tiina M. Metso</name>
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<author><name sortKey="Tatlisumak, Turgut" sort="Tatlisumak, Turgut" uniqKey="Tatlisumak T" first="Turgut" last="Tatlisumak">Turgut Tatlisumak</name>
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<author><name sortKey="Parati, Eugenio A" sort="Parati, Eugenio A" uniqKey="Parati E" first="Eugenio A." last="Parati">Eugenio A. Parati</name>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>University of Lund</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bevan, Steve" sort="Bevan, Steve" uniqKey="Bevan S" first="Steve" last="Bevan">Steve Bevan</name>
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<author><name sortKey="Sudlow, Cathie" sort="Sudlow, Cathie" uniqKey="Sudlow C" first="Cathie" last="Sudlow">Cathie Sudlow</name>
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<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
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<author><name sortKey="Walters, Matthew R" sort="Walters, Matthew R" uniqKey="Walters M" first="Matthew R" last="Walters">Matthew R. Walters</name>
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<author><name sortKey="Jannes, Jim" sort="Jannes, Jim" uniqKey="Jannes J" first="Jim" last="Jannes">Jim Jannes</name>
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</author>
<author><name sortKey="Shen, Jess" sort="Shen, Jess" uniqKey="Shen J" first="Jess" last="Shen">Jess Shen</name>
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<author><name sortKey="Crosslin, David" sort="Crosslin, David" uniqKey="Crosslin D" first="David" last="Crosslin">David Crosslin</name>
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</affiliation>
</author>
<author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<affiliation wicri:level="2"><nlm:aff id="A38">The University of Texas Health Science Center at Houston, Houston, Texas</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>The University of Texas Health Science Center at Houston, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H." last="Mosley">Thomas H. Mosley</name>
<affiliation wicri:level="2"><nlm:aff id="A39">University of Mississippi Medical Center, Jackson, MS</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État du Mississippi</region>
</placeName>
<wicri:cityArea>University of Mississippi Medical Center, Jackson</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hopewell, Jemma C" sort="Hopewell, Jemma C" uniqKey="Hopewell J" first="Jemma C." last="Hopewell">Jemma C. Hopewell</name>
<affiliation wicri:level="4"><nlm:aff id="A40">University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
</author>
<author><name sortKey="Strauch, Konstantin" sort="Strauch, Konstantin" uniqKey="Strauch K" first="Konstantin" last="Strauch">Konstantin Strauch</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A42">Partner site Munich Heart Alliance, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner site Munich Heart Alliance, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A50">University Hospital Grosshadern, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University Hospital Grosshadern, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Waldenberger, Melanie" sort="Waldenberger, Melanie" uniqKey="Waldenberger M" first="Melanie" last="Waldenberger">Melanie Waldenberger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A42">Partner site Munich Heart Alliance, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Partner site Munich Heart Alliance, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meisinger, Christine" sort="Meisinger, Christine" uniqKey="Meisinger C" first="Christine" last="Meisinger">Christine Meisinger</name>
<affiliation wicri:level="1"><nlm:aff id="A41">Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M. Arfan" last="Ikram">M. Arfan Ikram</name>
<affiliation wicri:level="1"><nlm:aff id="A43">Erasmus University Medical Center Rotterdam, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Erasmus University Medical Center Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Longstreth, Wt" sort="Longstreth, Wt" uniqKey="Longstreth W" first="Wt" last="Longstreth">Wt Longstreth</name>
<affiliation wicri:level="2"><nlm:aff id="A35">University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Meschia, James F" sort="Meschia, James F" uniqKey="Meschia J" first="James F." last="Meschia">James F. Meschia</name>
<affiliation wicri:level="2"><nlm:aff id="A44">Mayo Clinic, Florida</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Floride</region>
</placeName>
<wicri:cityArea>Mayo Clinic</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation wicri:level="2"><nlm:aff id="A45">Boston University School of Medicine, Boston, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Boston University School of Medicine, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sharma, Pankaj" sort="Sharma, Pankaj" uniqKey="Sharma P" first="Pankaj" last="Sharma">Pankaj Sharma</name>
<affiliation wicri:level="4"><nlm:aff id="A46">Royal Holloway, University of London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Royal Holloway, University of London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">Université de Londres</orgName>
</affiliation>
</author>
<author><name sortKey="Worrall, Bradford" sort="Worrall, Bradford" uniqKey="Worrall B" first="Bradford" last="Worrall">Bradford Worrall</name>
<affiliation wicri:level="2"><nlm:aff id="A47">University of Virginia, Charlottesville, Virginia</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
<wicri:cityArea>University of Virginia, Charlottesville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jern, Christina" sort="Jern, Christina" uniqKey="Jern C" first="Christina" last="Jern">Christina Jern</name>
<affiliation wicri:level="1"><nlm:aff id="A3">The University of Gothenburg, Gothenburg, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>The University of Gothenburg, Gothenburg</wicri:regionArea>
<wicri:noRegion>Gothenburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Levi, Christopher" sort="Levi, Christopher" uniqKey="Levi C" first="Christopher" last="Levi">Christopher Levi</name>
<affiliation wicri:level="1"><nlm:aff id="A48">John Hunter Hospital, Newcastle, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>John Hunter Hospital, Newcastle</wicri:regionArea>
<wicri:noRegion>Newcastle</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dichgans, Martin" sort="Dichgans, Martin" uniqKey="Dichgans M" first="Martin" last="Dichgans">Martin Dichgans</name>
<affiliation wicri:level="4"><nlm:aff id="A9">Ludwig-Maximilians-Universität München, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Ludwig-Maximilians-Universität München, Munich</wicri:regionArea>
<placeName><region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
<settlement type="city">Munich</settlement>
</placeName>
<orgName type="university">Université Louis-et-Maximilien de Munich</orgName>
</affiliation>
</author>
<author><name sortKey="Boncoraglio, Giorgio B" sort="Boncoraglio, Giorgio B" uniqKey="Boncoraglio G" first="Giorgio B." last="Boncoraglio">Giorgio B. Boncoraglio</name>
<affiliation wicri:level="3"><nlm:aff id="A25">Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan</wicri:regionArea>
<placeName><settlement type="city">Milan</settlement>
<region nuts="2">Lombardie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Markus, Hugh S" sort="Markus, Hugh S" uniqKey="Markus H" first="Hugh S." last="Markus">Hugh S. Markus</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stephanie" last="Debette">Stephanie Debette</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A19">Lille University Hospital, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lille University Hospital</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A49">University Hospital of Bordeaux, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Hospital of Bordeaux</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rolfs, Arndt" sort="Rolfs, Arndt" uniqKey="Rolfs A" first="Arndt" last="Rolfs">Arndt Rolfs</name>
<affiliation wicri:level="1"><nlm:aff id="A4">University of Rostock, Rostock, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Rostock, Rostock</wicri:regionArea>
<wicri:noRegion>Rostock</wicri:noRegion>
<wicri:noRegion>Rostock</wicri:noRegion>
<wicri:noRegion>Rostock</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name>
<affiliation wicri:level="4"><nlm:aff id="A6">University of Cambridge, Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A11">Center for Non-communicable Diseases, Karachi, Pakistan</nlm:aff>
<country xml:lang="fr">Pakistan</country>
<wicri:regionArea>Center for Non-communicable Diseases, Karachi</wicri:regionArea>
<wicri:noRegion>Karachi</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A12">University of Pennsylvania, US</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Veterans Affairs Maryland Health Care System, Baltimore, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Veterans Affairs Maryland Health Care System, Baltimore</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">University of Maryland School of Medicine, Baltimore, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>University of Maryland School of Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Stroke; a journal of cerebral circulation</title>
<idno type="ISSN">0039-2499</idno>
<idno type="eISSN">1524-4628</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>African Continental Ancestry Group (genetics)</term>
<term>Age of Onset</term>
<term>Aged</term>
<term>Asian Continental Ancestry Group (genetics)</term>
<term>Brain Ischemia (complications)</term>
<term>Brain Ischemia (genetics)</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Computer Simulation</term>
<term>DNA, Intergenic (genetics)</term>
<term>European Continental Ancestry Group (genetics)</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Serine Endopeptidases (genetics)</term>
<term>Serine Endopeptidases (metabolism)</term>
<term>Stroke (etiology)</term>
<term>Stroke (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN intergénique (génétique)</term>
<term>Accident vasculaire cérébral (génétique)</term>
<term>Accident vasculaire cérébral (étiologie)</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Chromosomes humains de la paire 10</term>
<term>Encéphalopathie ischémique ()</term>
<term>Encéphalopathie ischémique (génétique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Population d'origine africaine (génétique)</term>
<term>Population d'origine asiatique (génétique)</term>
<term>Population d'origine européenne (génétique)</term>
<term>Prédisposition génétique à une maladie</term>
<term>Serine endopeptidases (génétique)</term>
<term>Serine endopeptidases (métabolisme)</term>
<term>Simulation numérique</term>
<term>Sujet âgé</term>
<term>Âge de début</term>
<term>Étude d'association pangénomique</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Intergenic</term>
<term>Serine Endopeptidases</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Brain Ischemia</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Stroke</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>African Continental Ancestry Group</term>
<term>Asian Continental Ancestry Group</term>
<term>Brain Ischemia</term>
<term>European Continental Ancestry Group</term>
<term>Stroke</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN intergénique</term>
<term>Accident vasculaire cérébral</term>
<term>Encéphalopathie ischémique</term>
<term>Population d'origine africaine</term>
<term>Population d'origine asiatique</term>
<term>Population d'origine européenne</term>
<term>Serine endopeptidases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Serine Endopeptidases</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Serine endopeptidases</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Accident vasculaire cérébral</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Age of Onset</term>
<term>Aged</term>
<term>Chromosomes, Human, Pair 10</term>
<term>Computer Simulation</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Odds Ratio</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Chromosomes humains de la paire 10</term>
<term>Encéphalopathie ischémique</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Odds ratio</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie</term>
<term>Simulation numérique</term>
<term>Sujet âgé</term>
<term>Âge de début</term>
<term>Étude d'association pangénomique</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background and Purpose</title>
<p id="P1">Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a two-stage meta-analysis of genome-wide association studies (GWAS), focusing on stroke cases with an age of onset < 60 years old.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">The Discovery stage of our GWAS included 4,505 cases and 21,968 controls of European, South-Asian and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10<sup>−6</sup>
and performed <italic>in silico</italic>
association analyses in an independent sample of up to 1,003 cases and 7,745 controls.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the Discovery and Follow-up Stages (rs11196288, OR=1.41, P=9.5×10<sup>−9</sup>
). The associated locus is in an intergenic region between <italic>TCF7L2</italic>
and <italic>HABP2</italic>
. In a further analysis in an independent sample, we found that two SNPs in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of <italic>HABP2</italic>
.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4"><italic>HABP2</italic>
, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.</p>
</sec>
</div>
</front>
</TEI>
</record>
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