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Serveur d'exploration sur les relations entre la France et l'Australie

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Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial STXBP5 and STX2

Identifieur interne : 002033 ( Pmc/Curation ); précédent : 002032; suivant : 002034

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial STXBP5 and STX2

Auteurs : Jie Huang [États-Unis] ; Jennifer E. Huffman [Royaume-Uni] ; Munekazu Yamkauchi [États-Unis] ; Stella Trompet [Pays-Bas] ; Folkert W. Asselbergs [Pays-Bas, Royaume-Uni] ; Maria Sabater-Lleal [Suède] ; David-Alexandre Trégouët [France] ; Wei-Min Chen [États-Unis] ; Nicholas L. Smith [États-Unis] ; Marcus E. Kleber [Allemagne] ; So-Youn Shin [Royaume-Uni] ; Diane M. Becker [États-Unis] ; Weihong Tang [États-Unis] ; Abbas Dehghan [Pays-Bas] ; Andrew D. Johnson [États-Unis] ; Vinh Truong [France] ; Lasse Folkersen [Suède] ; Qiong Yang [États-Unis] ; Tiphaine Oudot-Mellakh [France] ; Brendan M. Buckley [Irlande (pays)] ; Jason H. Moore [États-Unis] ; Frances M. K. Williams [Royaume-Uni] ; Harry Campbell [Royaume-Uni] ; Günther Silbernagel [Suisse] ; Veronique Vitart [Royaume-Uni] ; Igor Rudan [Royaume-Uni] ; Geoffrey H. Tofler [Australie] ; Gerjan J. Navis [Pays-Bas] ; Anita Destefano [États-Unis] ; Alan F. Wright [Royaume-Uni] ; Ming-Huei Chen [États-Unis] ; Anton J. M. De Craen [Pays-Bas] ; Bradford B. Worrall [États-Unis] ; Alicja R. Rudnicka [Royaume-Uni] ; Ann Rumley [Royaume-Uni] ; Ebony B. Bookman [États-Unis] ; Bruce M. Psaty [États-Unis] ; Fang Chen [États-Unis] ; Keith L. Keene [États-Unis] ; Oscar H. Franco [Pays-Bas] ; Bernhard O. Böhm [Allemagne] ; Andre G. Uitterlinden [Pays-Bas] ; Angela M. Carter [Royaume-Uni] ; J. Wouter Jukema [Pays-Bas] ; Naveed Sattar [Royaume-Uni] ; Joshua C. Bis [États-Unis] ; Mohammad A. Ikram [Pays-Bas] ; Michèle M. Sale [États-Unis] ; Barbara Mcknight [États-Unis] ; Myriam Fornage [États-Unis] ; Ian Ford [Royaume-Uni] ; Kent Taylor [États-Unis] ; P. Eline Slagboom [Pays-Bas] ; Wendy L. Mcardle [Royaume-Uni] ; Fang-Chi Hsu [États-Unis] ; Anders Franco-Cereceda [Suède] ; Alison H. Goodall [Royaume-Uni] ; Lisa R. Yanek [États-Unis] ; Karen L. Furie [États-Unis] ; Mary Cushman [États-Unis] ; Albert Hofman [Pays-Bas] ; Jacqueline Cm. Witteman [Pays-Bas] ; Aaron R. Folsom [États-Unis] ; Saonli Basu [États-Unis] ; Nena Matijevic [États-Unis] ; Wiek H. Van Gilst [Pays-Bas] ; James F. Wilson [Royaume-Uni] ; Rudi G. J. Westendorp [Pays-Bas] ; Sekar Kathiresan [États-Unis] ; Muredach P. Reilly [États-Unis] ; Russell P. Tracy [États-Unis] ; Ozren Polasek [Croatie] ; Bernhard R. Winkelmann [Allemagne] ; Peter J. Grant [Pays-Bas] ; Hans L. Hillege [Pays-Bas] ; Francois Cambien [France] ; David J. Stott [Royaume-Uni] ; Gordon D. Lowe [Royaume-Uni] ; Timothy D. Spector [Royaume-Uni] ; James B. Meigs [États-Unis] ; Winfried Marz [Allemagne] ; Per Eriksson [Suède] ; Lewis C. Becker [États-Unis] ; Pierre-Emmanuel Morange [France] ; Nicole Soranzo [Royaume-Uni] ; Scott M. Williams [États-Unis] ; Caroline Hayward [Royaume-Uni] ; Pim Van Der Harst [Pays-Bas] ; Anders Hamsten [Suède] ; Charles J. Lowenstein [États-Unis] ; David P. Strachan [Royaume-Uni] ; Christopher J. O'Donnell [États-Unis]

Source :

RBID : PMC:4009733

Abstract

Objective

Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA.

Approach and Results

Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P <5.0×10−8). The first locus is on 6q24.3, with the lead SNP (rs9399599, P=2.9×10−14) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739, P=1.3×10−9) is intronic to POLB and less than 200kb away from the tPA encoding gene PLAT. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r2 = 0.50) within exon 5 of PLAT (P=2.0×10−8). The third locus is on 12q24.33, with the lead SNP (rs7301826, P=1.0×10−9) within intron 7 of STX2. We further found evidence for association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased release of tPA from vascular endothelial cells, while silencing of STX2 increased tPA release. Through an in-silico lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke.

Conclusions

We identified three loci associated with circulating tPA levels, the PLAT region, STXBP5 and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.


Url:
DOI: 10.1161/ATVBAHA.113.302088
PubMed: 24578379
PubMed Central: 4009733

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Jie Huang
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
Andrew D. Johnson
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
Bernhard O. Böhm
<affiliation>
<nlm:aff id="A41">LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London</nlm:aff>
<wicri:noCountry code="subfield">Singapore and Imperial College London</wicri:noCountry>
</affiliation>
Winfried Marz
<affiliation>
<nlm:aff id="A74">Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria</nlm:aff>
<wicri:noCountry code="subfield">Graz Austria</wicri:noCountry>
</affiliation>
Christopher J. O'Donnell
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A64">Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiology Division, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>

Le document en format XML

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<name sortKey="Sabater Lleal, Maria" sort="Sabater Lleal, Maria" uniqKey="Sabater Lleal M" first="Maria" last="Sabater-Lleal">Maria Sabater-Lleal</name>
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<name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
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<name sortKey="Chen, Wei Min" sort="Chen, Wei Min" uniqKey="Chen W" first="Wei-Min" last="Chen">Wei-Min Chen</name>
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<name sortKey="Smith, Nicholas L" sort="Smith, Nicholas L" uniqKey="Smith N" first="Nicholas L." last="Smith">Nicholas L. Smith</name>
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<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
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<nlm:aff id="A15">Group Health Research Institute, Group Health Cooperative, Seattle WA 98101 USA</nlm:aff>
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<name sortKey="Kleber, Marcus E" sort="Kleber, Marcus E" uniqKey="Kleber M" first="Marcus E." last="Kleber">Marcus E. Kleber</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A18">Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim</wicri:regionArea>
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<author>
<name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name>
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<nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A20">MRC Centre for CAiTE, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for CAiTE, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
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<author>
<name sortKey="Becker, Diane M" sort="Becker, Diane M" uniqKey="Becker D" first="Diane M." last="Becker">Diane M. Becker</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
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</author>
<author>
<name sortKey="Tang, Weihong" sort="Tang, Weihong" uniqKey="Tang W" first="Weihong" last="Tang">Weihong Tang</name>
<affiliation wicri:level="1">
<nlm:aff id="A22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">ICAN Institute for Cardiometabolism and Nutrion, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrion, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Folkersen, Lasse" sort="Folkersen, Lasse" uniqKey="Folkersen L" first="Lasse" last="Folkersen">Lasse Folkersen</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Oudot Mellakh, Tiphaine" sort="Oudot Mellakh, Tiphaine" uniqKey="Oudot Mellakh T" first="Tiphaine" last="Oudot-Mellakh">Tiphaine Oudot-Mellakh</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M." last="Buckley">Brendan M. Buckley</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Department of Pharmacology and Therapeutics, University College Cork, Ireland</nlm:aff>
<country xml:lang="fr">Irlande (pays)</country>
<wicri:regionArea>Department of Pharmacology and Therapeutics, University College Cork</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moore, Jason H" sort="Moore, Jason H" uniqKey="Moore J" first="Jason H." last="Moore">Jason H. Moore</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A28">Department of Community and Family Medicine, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Community and Family Medicine, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Williams, Frances M K" sort="Williams, Frances M K" uniqKey="Williams F" first="Frances M. K." last="Williams">Frances M. K. Williams</name>
<affiliation wicri:level="1">
<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Silbernagel, Gunther" sort="Silbernagel, Gunther" uniqKey="Silbernagel G" first="Günther" last="Silbernagel">Günther Silbernagel</name>
<affiliation wicri:level="1">
<nlm:aff id="A31">Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tofler, Geoffrey H" sort="Tofler, Geoffrey H" uniqKey="Tofler G" first="Geoffrey H." last="Tofler">Geoffrey H. Tofler</name>
<affiliation wicri:level="1">
<nlm:aff id="A32">Royal North Shore Hospital, University of Sydney, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Royal North Shore Hospital, University of Sydney</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Navis, Gerjan J" sort="Navis, Gerjan J" uniqKey="Navis G" first="Gerjan J." last="Navis">Gerjan J. Navis</name>
<affiliation wicri:level="1">
<nlm:aff id="A33">Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Destefano, Anita" sort="Destefano, Anita" uniqKey="Destefano A" first="Anita" last="Destefano">Anita Destefano</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F." last="Wright">Alan F. Wright</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Ming Huei" sort="Chen, Ming Huei" uniqKey="Chen M" first="Ming-Huei" last="Chen">Ming-Huei Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="De Craen, Anton J M" sort="De Craen, Anton J M" uniqKey="De Craen A" first="Anton J. M." last="De Craen">Anton J. M. De Craen</name>
<affiliation wicri:level="1">
<nlm:aff id="A6">Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Gerontology and Geriatrics, Leiden University Medical Center</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Worrall, Bradford B" sort="Worrall, Bradford B" uniqKey="Worrall B" first="Bradford B." last="Worrall">Bradford B. Worrall</name>
<affiliation wicri:level="1">
<nlm:aff id="A13">Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rudnicka, Alicja R" sort="Rudnicka, Alicja R" uniqKey="Rudnicka A" first="Alicja R." last="Rudnicka">Alicja R. Rudnicka</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rumley, Ann" sort="Rumley, Ann" uniqKey="Rumley A" first="Ann" last="Rumley">Ann Rumley</name>
<affiliation wicri:level="1">
<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bookman, Ebony B" sort="Bookman, Ebony B" uniqKey="Bookman E" first="Ebony B." last="Bookman">Ebony B. Bookman</name>
<affiliation wicri:level="1">
<nlm:aff id="A36">Division of Genomic Medicine, NHGRI, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Genomic Medicine, NHGRI, Bethesda, MD</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A15">Group Health Research Institute, Group Health Cooperative, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Group Health Research Institute, Group Health Cooperative</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A37">Department of Medicine, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Washington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A38">Department of Health Services, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Health Services, University of Washington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Fang" sort="Chen, Fang" uniqKey="Chen F" first="Fang" last="Chen">Fang Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="A13">Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Keene, Keith L" sort="Keene, Keith L" uniqKey="Keene K" first="Keith L." last="Keene">Keith L. Keene</name>
<affiliation wicri:level="1">
<nlm:aff id="A39">Department of Biology and Center for Health Disparities Research, East Carolina University, Greenville, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biology and Center for Health Disparities Research, East Carolina University, Greenville, NC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Franco, Oscar H" sort="Franco, Oscar H" uniqKey="Franco O" first="Oscar H." last="Franco">Oscar H. Franco</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bohm, Bernhard O" sort="Bohm, Bernhard O" uniqKey="Bohm B" first="Bernhard O." last="Böhm">Bernhard O. Böhm</name>
<affiliation wicri:level="1">
<nlm:aff id="A40">Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine I, Ulm University Medical Centre, Ulm</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="A41">LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London</nlm:aff>
<wicri:noCountry code="subfield">Singapore and Imperial College London</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A42">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Carter, Angela M" sort="Carter, Angela M" uniqKey="Carter A" first="Angela M." last="Carter">Angela M. Carter</name>
<affiliation wicri:level="1">
<nlm:aff id="A43">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cardiovascular and Diabetes Research, Leeds University, Leeds</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J. Wouter" last="Jukema">J. Wouter Jukema</name>
<affiliation wicri:level="1">
<nlm:aff id="A5">Department of Cardiology, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, Leiden University Medical Center</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A44">Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Durrer Center for Cardiogenetic Research, Amsterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A45">Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Interuniversity Cardiology Institute of the Netherlands, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name>
<affiliation wicri:level="1">
<nlm:aff id="A46">BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow</wicri:regionArea>
</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="A37">Department of Medicine, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Washington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Ikram, Mohammad A" sort="Ikram, Mohammad A" uniqKey="Ikram M" first="Mohammad A." last="Ikram">Mohammad A. Ikram</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A47">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A48">Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sale, Michele M" sort="Sale, Michele M" uniqKey="Sale M" first="Michèle M." last="Sale">Michèle M. Sale</name>
<affiliation wicri:level="1">
<nlm:aff id="A49">Center for Public Health Genomics, Department of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington</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="1">
<nlm:aff id="A50">Brown Foundation Institute of Molecular Medicine and Human Genetics Center, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Brown Foundation Institute of Molecular Medicine and Human Genetics Center, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name>
<affiliation wicri:level="1">
<nlm:aff id="A51">Robertson Center for Biostatistics, University of Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Robertson Center for Biostatistics, University of Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Taylor, Kent" sort="Taylor, Kent" uniqKey="Taylor K" first="Kent" last="Taylor">Kent Taylor</name>
<affiliation wicri:level="1">
<nlm:aff id="A52">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A53">Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Epidemiology, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mcardle, Wendy L" sort="Mcardle, Wendy L" uniqKey="Mcardle W" first="Wendy L." last="Mcardle">Wendy L. Mcardle</name>
<affiliation wicri:level="1">
<nlm:aff id="A54">ALSPAC Laboratory, Department of Social Medicine, University of Bristol, Bristol BS8 2BN, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>ALSPAC Laboratory, Department of Social Medicine, University of Bristol, Bristol BS8 2BN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hsu, Fang Chi" sort="Hsu, Fang Chi" uniqKey="Hsu F" first="Fang-Chi" last="Hsu">Fang-Chi Hsu</name>
<affiliation wicri:level="1">
<nlm:aff id="A55">Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Franco Cereceda, Anders" sort="Franco Cereceda, Anders" uniqKey="Franco Cereceda A" first="Anders" last="Franco-Cereceda">Anders Franco-Cereceda</name>
<affiliation wicri:level="1">
<nlm:aff id="A56">Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H." last="Goodall">Alison H. Goodall</name>
<affiliation wicri:level="1">
<nlm:aff id="A57">Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yanek, Lisa R" sort="Yanek, Lisa R" uniqKey="Yanek L" first="Lisa R." last="Yanek">Lisa R. Yanek</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Furie, Karen L" sort="Furie, Karen L" uniqKey="Furie K" first="Karen L." last="Furie">Karen L. Furie</name>
<affiliation wicri:level="1">
<nlm:aff id="A58">The Warren Alpert Medical School of Brown University, Providence, RI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Warren Alpert Medical School of Brown University, Providence, RI</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cushman, Mary" sort="Cushman, Mary" uniqKey="Cushman M" first="Mary" last="Cushman">Mary Cushman</name>
<affiliation wicri:level="2">
<nlm:aff id="A59">Department of Medicine, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Vermont, Burlington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A60">Department of Pathology, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Vermont, Burlington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Witteman, Jacqueline Cm" sort="Witteman, Jacqueline Cm" uniqKey="Witteman J" first="Jacqueline Cm." last="Witteman">Jacqueline Cm. Witteman</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Folsom, Aaron R" sort="Folsom, Aaron R" uniqKey="Folsom A" first="Aaron R." last="Folsom">Aaron R. Folsom</name>
<affiliation wicri:level="1">
<nlm:aff id="A22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Basu, Saonli" sort="Basu, Saonli" uniqKey="Basu S" first="Saonli" last="Basu">Saonli Basu</name>
<affiliation wicri:level="1">
<nlm:aff id="A61">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Matijevic, Nena" sort="Matijevic, Nena" uniqKey="Matijevic N" first="Nena" last="Matijevic">Nena Matijevic</name>
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<nlm:aff id="A62">Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Van Gilst, Wiek H" sort="Van Gilst, Wiek H" uniqKey="Van Gilst W" first="Wiek H." last="Van Gilst">Wiek H. Van Gilst</name>
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<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
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</author>
<author>
<name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F." last="Wilson">James F. Wilson</name>
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<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
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<author>
<name sortKey="Westendorp, Rudi G J" sort="Westendorp, Rudi G J" uniqKey="Westendorp R" first="Rudi G. J." last="Westendorp">Rudi G. J. Westendorp</name>
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<nlm:aff id="A6">Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Gerontology and Geriatrics, Leiden University Medical Center</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
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</author>
<author>
<name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name>
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<nlm:aff id="A64">Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiology Division, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A65">Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A66">Center for Human Genetic Research,Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Human Genetic Research,Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A67">Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA</wicri:regionArea>
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<author>
<name sortKey="Reilly, Muredach P" sort="Reilly, Muredach P" uniqKey="Reilly M" first="Muredach P." last="Reilly">Muredach P. Reilly</name>
<affiliation wicri:level="1">
<nlm:aff id="A68">The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA</wicri:regionArea>
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<author>
<name sortKey="Tracy, Russell P" sort="Tracy, Russell P" uniqKey="Tracy R" first="Russell P." last="Tracy">Russell P. Tracy</name>
<affiliation wicri:level="2">
<nlm:aff id="A60">Department of Pathology, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Vermont, Burlington</wicri:cityArea>
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</author>
<author>
<name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name>
<affiliation wicri:level="1">
<nlm:aff id="A69">Department of Public Health, Faculty of Medicine, University of Split, Croatia</nlm:aff>
<country xml:lang="fr">Croatie</country>
<wicri:regionArea>Department of Public Health, Faculty of Medicine, University of Split</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Winkelmann, Bernhard R" sort="Winkelmann, Bernhard R" uniqKey="Winkelmann B" first="Bernhard R." last="Winkelmann">Bernhard R. Winkelmann</name>
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<nlm:aff id="A70">Cardiology Team Sachsenhausen, Frankfurt am Main, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cardiology Team Sachsenhausen, Frankfurt am Main</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Grant, Peter J" sort="Grant, Peter J" uniqKey="Grant P" first="Peter J." last="Grant">Peter J. Grant</name>
<affiliation wicri:level="1">
<nlm:aff id="A42">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hillege, Hans L" sort="Hillege, Hans L" uniqKey="Hillege H" first="Hans L." last="Hillege">Hans L. Hillege</name>
<affiliation wicri:level="1">
<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">ICAN Institute for Cardiometabolism and Nutrion, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrion, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Stott, David J" sort="Stott, David J" uniqKey="Stott D" first="David J." last="Stott">David J. Stott</name>
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<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
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</author>
<author>
<name sortKey="Lowe, Gordon D" sort="Lowe, Gordon D" uniqKey="Lowe G" first="Gordon D." last="Lowe">Gordon D. Lowe</name>
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<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
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</author>
<author>
<name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D." last="Spector">Timothy D. Spector</name>
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<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
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<author>
<name sortKey="Meigs, James B" sort="Meigs, James B" uniqKey="Meigs J" first="James B." last="Meigs">James B. Meigs</name>
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<nlm:aff id="A71">General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A72">Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115</wicri:regionArea>
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<name sortKey="Marz, Winfried" sort="Marz, Winfried" uniqKey="Marz W" first="Winfried" last="Marz">Winfried Marz</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A73">Synlab Academy, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Synlab Academy, Mannheim</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="A74">Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria</nlm:aff>
<wicri:noCountry code="subfield">Graz Austria</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
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<author>
<name sortKey="Becker, Lewis C" sort="Becker, Lewis C" uniqKey="Becker L" first="Lewis C." last="Becker">Lewis C. Becker</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
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</author>
<author>
<name sortKey="Morange, Pierre Emmanuel" sort="Morange, Pierre Emmanuel" uniqKey="Morange P" first="Pierre-Emmanuel" last="Morange">Pierre-Emmanuel Morange</name>
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<nlm:aff id="A75">INSERM UMRS_1062, Aix-Marseille Université, Marseille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMRS_1062, Aix-Marseille Université, Marseille</wicri:regionArea>
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</author>
<author>
<name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name>
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<nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Williams, Scott M" sort="Williams, Scott M" uniqKey="Williams S" first="Scott M." last="Williams">Scott M. Williams</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
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<name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
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<name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name>
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<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
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<name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
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</author>
<author>
<name sortKey="Lowenstein, Charles J" sort="Lowenstein, Charles J" uniqKey="Lowenstein C" first="Charles J." last="Lowenstein">Charles J. Lowenstein</name>
<affiliation wicri:level="2">
<nlm:aff id="A4">The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">État de New York</region>
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<author>
<name sortKey="Strachan, David P" sort="Strachan, David P" uniqKey="Strachan D" first="David P." last="Strachan">David P. Strachan</name>
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<nlm:aff id="A34">Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE, UK</nlm:aff>
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<wicri:regionArea>Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE</wicri:regionArea>
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<name sortKey="O Donnell, Christopher J" sort="O Donnell, Christopher J" uniqKey="O Donnell C" first="Christopher J." last="O'Donnell">Christopher J. O'Donnell</name>
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<nlm:aff id="A1">National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</nlm:aff>
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<region type="state">Massachusetts</region>
</placeName>
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<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A64">Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiology Division, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
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and
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<name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
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<nlm:aff id="A1">National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</nlm:aff>
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<author>
<name sortKey="Huffman, Jennifer E" sort="Huffman, Jennifer E" uniqKey="Huffman J" first="Jennifer E." last="Huffman">Jennifer E. Huffman</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
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<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
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<name sortKey="Yamkauchi, Munekazu" sort="Yamkauchi, Munekazu" uniqKey="Yamkauchi M" first="Munekazu" last="Yamkauchi">Munekazu Yamkauchi</name>
<affiliation wicri:level="2">
<nlm:aff id="A4">The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">État de New York</region>
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<wicri:cityArea>The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester</wicri:cityArea>
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<name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name>
<affiliation wicri:level="1">
<nlm:aff id="A5">Department of Cardiology, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, Leiden University Medical Center</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A6">Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Gerontology and Geriatrics, Leiden University Medical Center</wicri:regionArea>
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<name sortKey="Asselbergs, Folkert W" sort="Asselbergs, Folkert W" uniqKey="Asselbergs F" first="Folkert W." last="Asselbergs">Folkert W. Asselbergs</name>
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<nlm:aff id="A7">Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A8">Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</nlm:aff>
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<wicri:regionArea>Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A9">Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London</wicri:regionArea>
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<author>
<name sortKey="Sabater Lleal, Maria" sort="Sabater Lleal, Maria" uniqKey="Sabater Lleal M" first="Maria" last="Sabater-Lleal">Maria Sabater-Lleal</name>
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<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name>
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<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">ICAN Institute for Cardiometabolism and Nutrion, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrion, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Wei Min" sort="Chen, Wei Min" uniqKey="Chen W" first="Wei-Min" last="Chen">Wei-Min Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="A13">Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Smith, Nicholas L" sort="Smith, Nicholas L" uniqKey="Smith N" first="Nicholas L." last="Smith">Nicholas L. Smith</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A15">Group Health Research Institute, Group Health Cooperative, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Group Health Research Institute, Group Health Cooperative</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A16">Seattle Epidemiologic Research & Information Center, VA Office of Research & Development, Seattle WA 98108, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Seattle Epidemiologic Research & Information Center, VA Office of Research & Development, Seattle WA 98108</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kleber, Marcus E" sort="Kleber, Marcus E" uniqKey="Kleber M" first="Marcus E." last="Kleber">Marcus E. Kleber</name>
<affiliation wicri:level="1">
<nlm:aff id="A17">Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A18">Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Shin, So Youn" sort="Shin, So Youn" uniqKey="Shin S" first="So-Youn" last="Shin">So-Youn Shin</name>
<affiliation wicri:level="1">
<nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A20">MRC Centre for CAiTE, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for CAiTE, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Becker, Diane M" sort="Becker, Diane M" uniqKey="Becker D" first="Diane M." last="Becker">Diane M. Becker</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Tang, Weihong" sort="Tang, Weihong" uniqKey="Tang W" first="Weihong" last="Tang">Weihong Tang</name>
<affiliation wicri:level="1">
<nlm:aff id="A22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">ICAN Institute for Cardiometabolism and Nutrion, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrion, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Folkersen, Lasse" sort="Folkersen, Lasse" uniqKey="Folkersen L" first="Lasse" last="Folkersen">Lasse Folkersen</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Oudot Mellakh, Tiphaine" sort="Oudot Mellakh, Tiphaine" uniqKey="Oudot Mellakh T" first="Tiphaine" last="Oudot-Mellakh">Tiphaine Oudot-Mellakh</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M." last="Buckley">Brendan M. Buckley</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Department of Pharmacology and Therapeutics, University College Cork, Ireland</nlm:aff>
<country xml:lang="fr">Irlande (pays)</country>
<wicri:regionArea>Department of Pharmacology and Therapeutics, University College Cork</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moore, Jason H" sort="Moore, Jason H" uniqKey="Moore J" first="Jason H." last="Moore">Jason H. Moore</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A28">Department of Community and Family Medicine, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Community and Family Medicine, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Williams, Frances M K" sort="Williams, Frances M K" uniqKey="Williams F" first="Frances M. K." last="Williams">Frances M. K. Williams</name>
<affiliation wicri:level="1">
<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Campbell, Harry" sort="Campbell, Harry" uniqKey="Campbell H" first="Harry" last="Campbell">Harry Campbell</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Silbernagel, Gunther" sort="Silbernagel, Gunther" uniqKey="Silbernagel G" first="Günther" last="Silbernagel">Günther Silbernagel</name>
<affiliation wicri:level="1">
<nlm:aff id="A31">Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Vitart, Veronique" sort="Vitart, Veronique" uniqKey="Vitart V" first="Veronique" last="Vitart">Veronique Vitart</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rudan, Igor" sort="Rudan, Igor" uniqKey="Rudan I" first="Igor" last="Rudan">Igor Rudan</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tofler, Geoffrey H" sort="Tofler, Geoffrey H" uniqKey="Tofler G" first="Geoffrey H." last="Tofler">Geoffrey H. Tofler</name>
<affiliation wicri:level="1">
<nlm:aff id="A32">Royal North Shore Hospital, University of Sydney, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Royal North Shore Hospital, University of Sydney</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Navis, Gerjan J" sort="Navis, Gerjan J" uniqKey="Navis G" first="Gerjan J." last="Navis">Gerjan J. Navis</name>
<affiliation wicri:level="1">
<nlm:aff id="A33">Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Destefano, Anita" sort="Destefano, Anita" uniqKey="Destefano A" first="Anita" last="Destefano">Anita Destefano</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wright, Alan F" sort="Wright, Alan F" uniqKey="Wright A" first="Alan F." last="Wright">Alan F. Wright</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Ming Huei" sort="Chen, Ming Huei" uniqKey="Chen M" first="Ming-Huei" last="Chen">Ming-Huei Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Biostatistics, Boston University, Boston, Mass, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University, Boston, Mass</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="De Craen, Anton J M" sort="De Craen, Anton J M" uniqKey="De Craen A" first="Anton J. M." last="De Craen">Anton J. M. De Craen</name>
<affiliation wicri:level="1">
<nlm:aff id="A6">Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Gerontology and Geriatrics, Leiden University Medical Center</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Worrall, Bradford B" sort="Worrall, Bradford B" uniqKey="Worrall B" first="Bradford B." last="Worrall">Bradford B. Worrall</name>
<affiliation wicri:level="1">
<nlm:aff id="A13">Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rudnicka, Alicja R" sort="Rudnicka, Alicja R" uniqKey="Rudnicka A" first="Alicja R." last="Rudnicka">Alicja R. Rudnicka</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rumley, Ann" sort="Rumley, Ann" uniqKey="Rumley A" first="Ann" last="Rumley">Ann Rumley</name>
<affiliation wicri:level="1">
<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bookman, Ebony B" sort="Bookman, Ebony B" uniqKey="Bookman E" first="Ebony B." last="Bookman">Ebony B. Bookman</name>
<affiliation wicri:level="1">
<nlm:aff id="A36">Division of Genomic Medicine, NHGRI, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Genomic Medicine, NHGRI, Bethesda, MD</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A15">Group Health Research Institute, Group Health Cooperative, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Group Health Research Institute, Group Health Cooperative</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A37">Department of Medicine, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Washington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A38">Department of Health Services, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Health Services, University of Washington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Chen, Fang" sort="Chen, Fang" uniqKey="Chen F" first="Fang" last="Chen">Fang Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="A13">Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Keene, Keith L" sort="Keene, Keith L" uniqKey="Keene K" first="Keith L." last="Keene">Keith L. Keene</name>
<affiliation wicri:level="1">
<nlm:aff id="A39">Department of Biology and Center for Health Disparities Research, East Carolina University, Greenville, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biology and Center for Health Disparities Research, East Carolina University, Greenville, NC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Franco, Oscar H" sort="Franco, Oscar H" uniqKey="Franco O" first="Oscar H." last="Franco">Oscar H. Franco</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bohm, Bernhard O" sort="Bohm, Bernhard O" uniqKey="Bohm B" first="Bernhard O." last="Böhm">Bernhard O. Böhm</name>
<affiliation wicri:level="1">
<nlm:aff id="A40">Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine I, Ulm University Medical Centre, Ulm</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="A41">LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London</nlm:aff>
<wicri:noCountry code="subfield">Singapore and Imperial College London</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A42">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Carter, Angela M" sort="Carter, Angela M" uniqKey="Carter A" first="Angela M." last="Carter">Angela M. Carter</name>
<affiliation wicri:level="1">
<nlm:aff id="A43">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cardiovascular and Diabetes Research, Leeds University, Leeds</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J. Wouter" last="Jukema">J. Wouter Jukema</name>
<affiliation wicri:level="1">
<nlm:aff id="A5">Department of Cardiology, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, Leiden University Medical Center</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A44">Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Durrer Center for Cardiogenetic Research, Amsterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A45">Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Interuniversity Cardiology Institute of the Netherlands, Utrecht</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name>
<affiliation wicri:level="1">
<nlm:aff id="A46">BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow</wicri:regionArea>
</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="A37">Department of Medicine, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Washington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Ikram, Mohammad A" sort="Ikram, Mohammad A" uniqKey="Ikram M" first="Mohammad A." last="Ikram">Mohammad A. Ikram</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A47">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A48">Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sale, Michele M" sort="Sale, Michele M" uniqKey="Sale M" first="Michèle M." last="Sale">Michèle M. Sale</name>
<affiliation wicri:level="1">
<nlm:aff id="A49">Center for Public Health Genomics, Department of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Public Health Genomics, Department of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">Department of Epidemiology, University of Washington, Seattle WA 98101 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington</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="1">
<nlm:aff id="A50">Brown Foundation Institute of Molecular Medicine and Human Genetics Center, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Brown Foundation Institute of Molecular Medicine and Human Genetics Center, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name>
<affiliation wicri:level="1">
<nlm:aff id="A51">Robertson Center for Biostatistics, University of Glasgow, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Robertson Center for Biostatistics, University of Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Taylor, Kent" sort="Taylor, Kent" uniqKey="Taylor K" first="Kent" last="Taylor">Kent Taylor</name>
<affiliation wicri:level="1">
<nlm:aff id="A52">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A53">Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Molecular Epidemiology, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mcardle, Wendy L" sort="Mcardle, Wendy L" uniqKey="Mcardle W" first="Wendy L." last="Mcardle">Wendy L. Mcardle</name>
<affiliation wicri:level="1">
<nlm:aff id="A54">ALSPAC Laboratory, Department of Social Medicine, University of Bristol, Bristol BS8 2BN, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>ALSPAC Laboratory, Department of Social Medicine, University of Bristol, Bristol BS8 2BN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hsu, Fang Chi" sort="Hsu, Fang Chi" uniqKey="Hsu F" first="Fang-Chi" last="Hsu">Fang-Chi Hsu</name>
<affiliation wicri:level="1">
<nlm:aff id="A55">Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Franco Cereceda, Anders" sort="Franco Cereceda, Anders" uniqKey="Franco Cereceda A" first="Anders" last="Franco-Cereceda">Anders Franco-Cereceda</name>
<affiliation wicri:level="1">
<nlm:aff id="A56">Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H." last="Goodall">Alison H. Goodall</name>
<affiliation wicri:level="1">
<nlm:aff id="A57">Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yanek, Lisa R" sort="Yanek, Lisa R" uniqKey="Yanek L" first="Lisa R." last="Yanek">Lisa R. Yanek</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Furie, Karen L" sort="Furie, Karen L" uniqKey="Furie K" first="Karen L." last="Furie">Karen L. Furie</name>
<affiliation wicri:level="1">
<nlm:aff id="A58">The Warren Alpert Medical School of Brown University, Providence, RI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Warren Alpert Medical School of Brown University, Providence, RI</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cushman, Mary" sort="Cushman, Mary" uniqKey="Cushman M" first="Mary" last="Cushman">Mary Cushman</name>
<affiliation wicri:level="2">
<nlm:aff id="A59">Department of Medicine, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Vermont, Burlington</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A60">Department of Pathology, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Vermont, Burlington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Witteman, Jacqueline Cm" sort="Witteman, Jacqueline Cm" uniqKey="Witteman J" first="Jacqueline Cm." last="Witteman">Jacqueline Cm. Witteman</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Folsom, Aaron R" sort="Folsom, Aaron R" uniqKey="Folsom A" first="Aaron R." last="Folsom">Aaron R. Folsom</name>
<affiliation wicri:level="1">
<nlm:aff id="A22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Basu, Saonli" sort="Basu, Saonli" uniqKey="Basu S" first="Saonli" last="Basu">Saonli Basu</name>
<affiliation wicri:level="1">
<nlm:aff id="A61">Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Biostatistics, University of Minnesota, Minneapolis, MN</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Matijevic, Nena" sort="Matijevic, Nena" uniqKey="Matijevic N" first="Nena" last="Matijevic">Nena Matijevic</name>
<affiliation wicri:level="1">
<nlm:aff id="A62">Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, Texas, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, Texas</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Gilst, Wiek H" sort="Van Gilst, Wiek H" uniqKey="Van Gilst W" first="Wiek H." last="Van Gilst">Wiek H. Van Gilst</name>
<affiliation wicri:level="1">
<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wilson, James F" sort="Wilson, James F" uniqKey="Wilson J" first="James F." last="Wilson">James F. Wilson</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Westendorp, Rudi G J" sort="Westendorp, Rudi G J" uniqKey="Westendorp R" first="Rudi G. J." last="Westendorp">Rudi G. J. Westendorp</name>
<affiliation wicri:level="1">
<nlm:aff id="A6">Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Gerontology and Geriatrics, Leiden University Medical Center</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name>
<affiliation wicri:level="1">
<nlm:aff id="A64">Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiology Division, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A65">Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A66">Center for Human Genetic Research,Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Human Genetic Research,Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A67">Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Reilly, Muredach P" sort="Reilly, Muredach P" uniqKey="Reilly M" first="Muredach P." last="Reilly">Muredach P. Reilly</name>
<affiliation wicri:level="1">
<nlm:aff id="A68">The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Tracy, Russell P" sort="Tracy, Russell P" uniqKey="Tracy R" first="Russell P." last="Tracy">Russell P. Tracy</name>
<affiliation wicri:level="2">
<nlm:aff id="A60">Department of Pathology, University of Vermont, Burlington, VT 05405 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Vermont</region>
</placeName>
<wicri:cityArea>Department of Pathology, University of Vermont, Burlington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Polasek, Ozren" sort="Polasek, Ozren" uniqKey="Polasek O" first="Ozren" last="Polasek">Ozren Polasek</name>
<affiliation wicri:level="1">
<nlm:aff id="A69">Department of Public Health, Faculty of Medicine, University of Split, Croatia</nlm:aff>
<country xml:lang="fr">Croatie</country>
<wicri:regionArea>Department of Public Health, Faculty of Medicine, University of Split</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Winkelmann, Bernhard R" sort="Winkelmann, Bernhard R" uniqKey="Winkelmann B" first="Bernhard R." last="Winkelmann">Bernhard R. Winkelmann</name>
<affiliation wicri:level="1">
<nlm:aff id="A70">Cardiology Team Sachsenhausen, Frankfurt am Main, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Cardiology Team Sachsenhausen, Frankfurt am Main</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Grant, Peter J" sort="Grant, Peter J" uniqKey="Grant P" first="Peter J." last="Grant">Peter J. Grant</name>
<affiliation wicri:level="1">
<nlm:aff id="A42">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hillege, Hans L" sort="Hillege, Hans L" uniqKey="Hillege H" first="Hans L." last="Hillege">Hans L. Hillege</name>
<affiliation wicri:level="1">
<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name>
<affiliation wicri:level="1">
<nlm:aff id="A11">INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">ICAN Institute for Cardiometabolism and Nutrion, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>ICAN Institute for Cardiometabolism and Nutrion, Paris</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Stott, David J" sort="Stott, David J" uniqKey="Stott D" first="David J." last="Stott">David J. Stott</name>
<affiliation wicri:level="1">
<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lowe, Gordon D" sort="Lowe, Gordon D" uniqKey="Lowe G" first="Gordon D." last="Lowe">Gordon D. Lowe</name>
<affiliation wicri:level="1">
<nlm:aff id="A35">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D." last="Spector">Timothy D. Spector</name>
<affiliation wicri:level="1">
<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Meigs, James B" sort="Meigs, James B" uniqKey="Meigs J" first="James B." last="Meigs">James B. Meigs</name>
<affiliation wicri:level="1">
<nlm:aff id="A71">General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A72">Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Marz, Winfried" sort="Marz, Winfried" uniqKey="Marz W" first="Winfried" last="Marz">Winfried Marz</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A73">Synlab Academy, Mannheim, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Synlab Academy, Mannheim</wicri:regionArea>
</affiliation>
<affiliation>
<nlm:aff id="A74">Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria</nlm:aff>
<wicri:noCountry code="subfield">Graz Austria</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Becker, Lewis C" sort="Becker, Lewis C" uniqKey="Becker L" first="Lewis C." last="Becker">Lewis C. Becker</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Morange, Pierre Emmanuel" sort="Morange, Pierre Emmanuel" uniqKey="Morange P" first="Pierre-Emmanuel" last="Morange">Pierre-Emmanuel Morange</name>
<affiliation wicri:level="1">
<nlm:aff id="A75">INSERM UMRS_1062, Aix-Marseille Université, Marseille, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMRS_1062, Aix-Marseille Université, Marseille</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name>
<affiliation wicri:level="1">
<nlm:aff id="A19">Wellcome Trust Sanger Institute, Hinxton, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A29">Department of Twin Research and Genetic Epidemiology, King's College London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Williams, Scott M" sort="Williams, Scott M" uniqKey="Williams S" first="Scott M." last="Williams">Scott M. Williams</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name>
<affiliation wicri:level="1">
<nlm:aff id="A63">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lowenstein, Charles J" sort="Lowenstein, Charles J" uniqKey="Lowenstein C" first="Charles J." last="Lowenstein">Charles J. Lowenstein</name>
<affiliation wicri:level="2">
<nlm:aff id="A4">The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Strachan, David P" sort="Strachan, David P" uniqKey="Strachan D" first="David P." last="Strachan">David P. Strachan</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="O Donnell, Christopher J" sort="O Donnell, Christopher J" uniqKey="O Donnell C" first="Christopher J." last="O'Donnell">Christopher J. O'Donnell</name>
<affiliation wicri:level="2">
<nlm:aff id="A1">National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="A2">National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</nlm:aff>
<wicri:noCountry code="subfield">Bethesda MD USA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A64">Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiology Division, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Arteriosclerosis, thrombosis, and vascular biology</title>
<idno type="ISSN">1079-5642</idno>
<idno type="eISSN">1524-4636</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Objective</title>
<p id="P3">Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA.</p>
</sec>
<sec id="S2">
<title>Approach and Results</title>
<p id="P4">Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (
<italic>P</italic>
<5.0×10
<sup>−8</sup>
). The first locus is on 6q24.3, with the lead SNP (rs9399599,
<italic>P</italic>
=2.9×10
<sup>−14</sup>
) within
<italic>STXBP5</italic>
. The second locus is on 8p11.21. The lead SNP (rs3136739,
<italic>P</italic>
=1.3×10
<sup>−9</sup>
) is intronic to
<italic>POLB</italic>
and less than 200kb away from the tPA encoding gene
<italic>PLAT</italic>
. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r
<sup>2</sup>
= 0.50) within exon 5 of
<italic>PLAT</italic>
(
<italic>P</italic>
=2.0×10
<sup>−8</sup>
). The third locus is on 12q24.33, with the lead SNP (rs7301826,
<italic>P</italic>
=1.0×10
<sup>−9</sup>
) within intron 7 of
<italic>STX2</italic>
. We further found evidence for association of lead SNPs in
<italic>STXBP5</italic>
and
<italic>STX2</italic>
with expression levels of the respective transcripts. In
<italic>in vitro</italic>
cell studies, silencing
<italic>STXBP5</italic>
decreased release of tPA from vascular endothelial cells, while silencing of
<italic>STX2</italic>
increased tPA release. Through an
<italic>in-silico</italic>
lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke.</p>
</sec>
<sec id="S3">
<title>Conclusions</title>
<p id="P5">We identified three loci associated with circulating tPA levels, the
<italic>PLAT</italic>
region,
<italic>STXBP5</italic>
and
<italic>STX2.</italic>
Our functional studies implicate a novel role for
<italic>STXBP5</italic>
and
<italic>STX2</italic>
in regulating tPA release.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">9505803</journal-id>
<journal-id journal-id-type="pubmed-jr-id">8623</journal-id>
<journal-id journal-id-type="nlm-ta">Arterioscler Thromb Vasc Biol</journal-id>
<journal-id journal-id-type="iso-abbrev">Arterioscler. Thromb. Vasc. Biol.</journal-id>
<journal-title-group>
<journal-title>Arteriosclerosis, thrombosis, and vascular biology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1079-5642</issn>
<issn pub-type="epub">1524-4636</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24578379</article-id>
<article-id pub-id-type="pmc">4009733</article-id>
<article-id pub-id-type="doi">10.1161/ATVBAHA.113.302088</article-id>
<article-id pub-id-type="manuscript">NIHMS567609</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial
<italic>STXBP5</italic>
and
<italic>STX2</italic>
</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Jie</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huffman</surname>
<given-names>Jennifer E.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yamkauchi</surname>
<given-names>Munekazu</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Trompet</surname>
<given-names>Stella</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Asselbergs</surname>
<given-names>Folkert W.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sabater-Lleal</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Trégouët</surname>
<given-names>David-Alexandre</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Wei-Min</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Smith</surname>
<given-names>Nicholas L.</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kleber</surname>
<given-names>Marcus E.</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shin</surname>
<given-names>So-Youn</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Becker</surname>
<given-names>Diane M.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tang</surname>
<given-names>Weihong</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dehghan</surname>
<given-names>Abbas</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Johnson</surname>
<given-names>Andrew D.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Truong</surname>
<given-names>Vinh</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Folkersen</surname>
<given-names>Lasse</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Qiong</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Oudot-Mellakh</surname>
<given-names>Tiphaine</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Buckley</surname>
<given-names>Brendan M.</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moore</surname>
<given-names>Jason H.</given-names>
</name>
<xref ref-type="aff" rid="A27">27</xref>
<xref ref-type="aff" rid="A28">28</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Williams</surname>
<given-names>Frances M.K.</given-names>
</name>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Campbell</surname>
<given-names>Harry</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Silbernagel</surname>
<given-names>Günther</given-names>
</name>
<xref ref-type="aff" rid="A31">31</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vitart</surname>
<given-names>Veronique</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rudan</surname>
<given-names>Igor</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tofler</surname>
<given-names>Geoffrey H.</given-names>
</name>
<xref ref-type="aff" rid="A32">32</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Navis</surname>
<given-names>Gerjan J.</given-names>
</name>
<xref ref-type="aff" rid="A33">33</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>DeStefano</surname>
<given-names>Anita</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wright</surname>
<given-names>Alan F.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Ming-Huei</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Craen</surname>
<given-names>Anton J.M.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Worrall</surname>
<given-names>Bradford B.</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rudnicka</surname>
<given-names>Alicja R.</given-names>
</name>
<xref ref-type="aff" rid="A34">34</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rumley</surname>
<given-names>Ann</given-names>
</name>
<xref ref-type="aff" rid="A35">35</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bookman</surname>
<given-names>Ebony B.</given-names>
</name>
<xref ref-type="aff" rid="A36">36</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Psaty</surname>
<given-names>Bruce M.</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
<xref ref-type="aff" rid="A37">37</xref>
<xref ref-type="aff" rid="A38">38</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Fang</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Keene</surname>
<given-names>Keith L.</given-names>
</name>
<xref ref-type="aff" rid="A39">39</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Franco</surname>
<given-names>Oscar H.</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Böhm</surname>
<given-names>Bernhard O.</given-names>
</name>
<xref ref-type="aff" rid="A40">40</xref>
<xref ref-type="aff" rid="A41">41</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Uitterlinden</surname>
<given-names>Andre G.</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
<xref ref-type="aff" rid="A42">42</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carter</surname>
<given-names>Angela M.</given-names>
</name>
<xref ref-type="aff" rid="A43">43</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jukema</surname>
<given-names>J. Wouter</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
<xref ref-type="aff" rid="A44">44</xref>
<xref ref-type="aff" rid="A45">45</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sattar</surname>
<given-names>Naveed</given-names>
</name>
<xref ref-type="aff" rid="A46">46</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bis</surname>
<given-names>Joshua C.</given-names>
</name>
<xref ref-type="aff" rid="A37">37</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ikram</surname>
<given-names>Mohammad A.</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
<xref ref-type="aff" rid="A47">47</xref>
<xref ref-type="aff" rid="A48">48</xref>
</contrib>
<contrib contrib-type="author">
<collab>the CHARGE consortium Neurology Working Group</collab>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sale</surname>
<given-names>Michèle M.</given-names>
</name>
<xref ref-type="aff" rid="A49">49</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McKnight</surname>
<given-names>Barbara</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fornage</surname>
<given-names>Myriam</given-names>
</name>
<xref ref-type="aff" rid="A50">50</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ford</surname>
<given-names>Ian</given-names>
</name>
<xref ref-type="aff" rid="A51">51</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Taylor</surname>
<given-names>Kent</given-names>
</name>
<xref ref-type="aff" rid="A52">52</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Slagboom</surname>
<given-names>P. Eline</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
<xref ref-type="aff" rid="A53">53</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McArdle</surname>
<given-names>Wendy L.</given-names>
</name>
<xref ref-type="aff" rid="A54">54</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hsu</surname>
<given-names>Fang-Chi</given-names>
</name>
<xref ref-type="aff" rid="A55">55</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Franco-Cereceda</surname>
<given-names>Anders</given-names>
</name>
<xref ref-type="aff" rid="A56">56</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Goodall</surname>
<given-names>Alison H.</given-names>
</name>
<xref ref-type="aff" rid="A57">57</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yanek</surname>
<given-names>Lisa R.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Furie</surname>
<given-names>Karen L.</given-names>
</name>
<xref ref-type="aff" rid="A58">58</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cushman</surname>
<given-names>Mary</given-names>
</name>
<xref ref-type="aff" rid="A59">59</xref>
<xref ref-type="aff" rid="A60">60</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hofman</surname>
<given-names>Albert</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Witteman</surname>
<given-names>Jacqueline CM.</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Folsom</surname>
<given-names>Aaron R.</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Basu</surname>
<given-names>Saonli</given-names>
</name>
<xref ref-type="aff" rid="A61">61</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Matijevic</surname>
<given-names>Nena</given-names>
</name>
<xref ref-type="aff" rid="A62">62</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van Gilst</surname>
<given-names>Wiek H.</given-names>
</name>
<xref ref-type="aff" rid="A63">63</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>James F.</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Westendorp</surname>
<given-names>Rudi G.J.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kathiresan</surname>
<given-names>Sekar</given-names>
</name>
<xref ref-type="aff" rid="A64">64</xref>
<xref ref-type="aff" rid="A65">65</xref>
<xref ref-type="aff" rid="A66">66</xref>
<xref ref-type="aff" rid="A67">67</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Reilly</surname>
<given-names>Muredach P.</given-names>
</name>
<xref ref-type="aff" rid="A68">68</xref>
</contrib>
<contrib contrib-type="author">
<collab>the CARDIoGRAM Consortium</collab>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tracy</surname>
<given-names>Russell P.</given-names>
</name>
<xref ref-type="aff" rid="A60">60</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Polasek</surname>
<given-names>Ozren</given-names>
</name>
<xref ref-type="aff" rid="A69">69</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Winkelmann</surname>
<given-names>Bernhard R.</given-names>
</name>
<xref ref-type="aff" rid="A70">70</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Grant</surname>
<given-names>Peter J.</given-names>
</name>
<xref ref-type="aff" rid="A42">42</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hillege</surname>
<given-names>Hans L.</given-names>
</name>
<xref ref-type="aff" rid="A63">63</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cambien</surname>
<given-names>Francois</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stott</surname>
<given-names>David J.</given-names>
</name>
<xref ref-type="aff" rid="A35">35</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lowe</surname>
<given-names>Gordon D.</given-names>
</name>
<xref ref-type="aff" rid="A35">35</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Spector</surname>
<given-names>Timothy D.</given-names>
</name>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Meigs</surname>
<given-names>James B.</given-names>
</name>
<xref ref-type="aff" rid="A71">71</xref>
<xref ref-type="aff" rid="A72">72</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marz</surname>
<given-names>Winfried</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
<xref ref-type="aff" rid="A73">73</xref>
<xref ref-type="aff" rid="A74">74</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eriksson</surname>
<given-names>Per</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Becker</surname>
<given-names>Lewis C.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Morange</surname>
<given-names>Pierre-Emmanuel</given-names>
</name>
<xref ref-type="aff" rid="A75">75</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Soranzo</surname>
<given-names>Nicole</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Williams</surname>
<given-names>Scott M.</given-names>
</name>
<xref ref-type="aff" rid="A27">27</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hayward</surname>
<given-names>Caroline</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van der Harst</surname>
<given-names>Pim</given-names>
</name>
<xref ref-type="aff" rid="A63">63</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hamsten</surname>
<given-names>Anders</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lowenstein</surname>
<given-names>Charles J.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Strachan</surname>
<given-names>David P.</given-names>
</name>
<xref ref-type="aff" rid="A34">34</xref>
<xref ref-type="author-notes" rid="FN2">**</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>O'Donnell</surname>
<given-names>Christopher J.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A64">64</xref>
<xref ref-type="author-notes" rid="FN2">**</xref>
</contrib>
<contrib contrib-type="author">
<collab>the CHARGE Consortium Hemostatic Factor Working Group</collab>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, MA USA</aff>
<aff id="A2">
<label>2</label>
National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda MD USA</aff>
<aff id="A3">
<label>3</label>
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK</aff>
<aff id="A4">
<label>4</label>
The Aab Cardiovascular Research Institute, Department of Medicine, The University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY USA</aff>
<aff id="A5">
<label>5</label>
Department of Cardiology, Leiden University Medical Center, The Netherlands</aff>
<aff id="A6">
<label>6</label>
Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands</aff>
<aff id="A7">
<label>7</label>
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands</aff>
<aff id="A8">
<label>8</label>
Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands</aff>
<aff id="A9">
<label>9</label>
Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom</aff>
<aff id="A10">
<label>10</label>
Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden</aff>
<aff id="A11">
<label>11</label>
INSERM UMR_S 937 ; Pierre et Marie Curie University, Paris, France</aff>
<aff id="A12">
<label>12</label>
ICAN Institute for Cardiometabolism and Nutrion, Paris, France</aff>
<aff id="A13">
<label>13</label>
Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA</aff>
<aff id="A14">
<label>14</label>
Department of Epidemiology, University of Washington, Seattle WA 98101 USA</aff>
<aff id="A15">
<label>15</label>
Group Health Research Institute, Group Health Cooperative, Seattle WA 98101 USA</aff>
<aff id="A16">
<label>16</label>
Seattle Epidemiologic Research & Information Center, VA Office of Research & Development, Seattle WA 98108, USA</aff>
<aff id="A17">
<label>17</label>
Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm, Germany</aff>
<aff id="A18">
<label>18</label>
Mannheim Institute of Public Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany</aff>
<aff id="A19">
<label>19</label>
Wellcome Trust Sanger Institute, Hinxton, United Kingdom</aff>
<aff id="A20">
<label>20</label>
MRC Centre for CAiTE, School of Social and Community Medicine, University of Bristol, Bristol, UK</aff>
<aff id="A21">
<label>21</label>
Johns Hopkins School of Medicine, Division of Internal Medicine, Baltimore, MD 21287 USA</aff>
<aff id="A22">
<label>22</label>
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA</aff>
<aff id="A23">
<label>23</label>
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A24">
<label>24</label>
Netherlands Consortium of Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands</aff>
<aff id="A25">
<label>25</label>
Department of Biostatistics, Boston University, Boston, Mass, USA</aff>
<aff id="A26">
<label>26</label>
Department of Pharmacology and Therapeutics, University College Cork, Ireland</aff>
<aff id="A27">
<label>27</label>
Departments of Genetics, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</aff>
<aff id="A28">
<label>28</label>
Department of Community and Family Medicine, Gesiel School of Medicine at Dartmouth, Lebanon, NH, USA</aff>
<aff id="A29">
<label>29</label>
Department of Twin Research and Genetic Epidemiology, King's College London, UK</aff>
<aff id="A30">
<label>30</label>
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK</aff>
<aff id="A31">
<label>31</label>
Department of Angiology, Swiss Cardiovascular Center, Inselspital Bern, Bern, Switzerland</aff>
<aff id="A32">
<label>32</label>
Royal North Shore Hospital, University of Sydney, Australia</aff>
<aff id="A33">
<label>33</label>
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</aff>
<aff id="A34">
<label>34</label>
Division of Population Health Sciences and Education, St George's University of London, London SW17 0RE, UK</aff>
<aff id="A35">
<label>35</label>
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</aff>
<aff id="A36">
<label>36</label>
Division of Genomic Medicine, NHGRI, Bethesda, MD, USA</aff>
<aff id="A37">
<label>37</label>
Department of Medicine, University of Washington, Seattle WA 98101 USA</aff>
<aff id="A38">
<label>38</label>
Department of Health Services, University of Washington, Seattle WA 98101 USA</aff>
<aff id="A39">
<label>39</label>
Department of Biology and Center for Health Disparities Research, East Carolina University, Greenville, NC, USA</aff>
<aff id="A40">
<label>40</label>
Department of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany</aff>
<aff id="A41">
<label>41</label>
LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London</aff>
<aff id="A42">
<label>42</label>
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A43">
<label>43</label>
Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, UK</aff>
<aff id="A44">
<label>44</label>
Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</aff>
<aff id="A45">
<label>45</label>
Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</aff>
<aff id="A46">
<label>46</label>
BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, United Kingdom</aff>
<aff id="A47">
<label>47</label>
Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A48">
<label>48</label>
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A49">
<label>49</label>
Center for Public Health Genomics, Department of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA</aff>
<aff id="A50">
<label>50</label>
Brown Foundation Institute of Molecular Medicine and Human Genetics Center, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA</aff>
<aff id="A51">
<label>51</label>
Robertson Center for Biostatistics, University of Glasgow, United Kingdom</aff>
<aff id="A52">
<label>52</label>
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA</aff>
<aff id="A53">
<label>53</label>
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</aff>
<aff id="A54">
<label>54</label>
ALSPAC Laboratory, Department of Social Medicine, University of Bristol, Bristol BS8 2BN, UK</aff>
<aff id="A55">
<label>55</label>
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff>
<aff id="A56">
<label>56</label>
Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</aff>
<aff id="A57">
<label>57</label>
Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom</aff>
<aff id="A58">
<label>58</label>
The Warren Alpert Medical School of Brown University, Providence, RI, USA</aff>
<aff id="A59">
<label>59</label>
Department of Medicine, University of Vermont, Burlington, VT 05405 USA</aff>
<aff id="A60">
<label>60</label>
Department of Pathology, University of Vermont, Burlington, VT 05405 USA</aff>
<aff id="A61">
<label>61</label>
Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA</aff>
<aff id="A62">
<label>62</label>
Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, Texas, USA</aff>
<aff id="A63">
<label>63</label>
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands</aff>
<aff id="A64">
<label>64</label>
Cardiology Division, Massachusetts General Hospital, Boston, MA, USA</aff>
<aff id="A65">
<label>65</label>
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA</aff>
<aff id="A66">
<label>66</label>
Center for Human Genetic Research,Massachusetts General Hospital, Boston, MA, USA</aff>
<aff id="A67">
<label>67</label>
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA</aff>
<aff id="A68">
<label>68</label>
The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA</aff>
<aff id="A69">
<label>69</label>
Department of Public Health, Faculty of Medicine, University of Split, Croatia</aff>
<aff id="A70">
<label>70</label>
Cardiology Team Sachsenhausen, Frankfurt am Main, Germany</aff>
<aff id="A71">
<label>71</label>
General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA</aff>
<aff id="A72">
<label>72</label>
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA</aff>
<aff id="A73">
<label>73</label>
Synlab Academy, Mannheim, Germany</aff>
<aff id="A74">
<label>74</label>
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria</aff>
<aff id="A75">
<label>75</label>
INSERM UMRS_1062, Aix-Marseille Université, Marseille, France</aff>
<author-notes>
<corresp id="cor1">
<bold>Corresponding author</bold>
:Christopher J. O'Donnell, MD MPH, Address: National Heart, Lung and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Street, 2nd Floor, Framingham, MA 01702,
<email>odonnellc@nhlbi.nih.gov</email>
, Telephone: (508) 935-3419</corresp>
<fn id="FN1" fn-type="equal">
<label>*</label>
<p id="P1">These first authors contributed equally</p>
</fn>
<fn id="FN2" fn-type="equal">
<label>**</label>
<p id="P2">These last authors contributed equally</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>31</day>
<month>3</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>27</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>5</month>
<year>2015</year>
</pub-date>
<volume>34</volume>
<issue>5</issue>
<fpage>1093</fpage>
<lpage>1101</lpage>
<pmc-comment>elocation-id from pubmed: 10.1161/ATVBAHA.113.302088</pmc-comment>
<abstract>
<sec id="S1">
<title>Objective</title>
<p id="P3">Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA.</p>
</sec>
<sec id="S2">
<title>Approach and Results</title>
<p id="P4">Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (
<italic>P</italic>
<5.0×10
<sup>−8</sup>
). The first locus is on 6q24.3, with the lead SNP (rs9399599,
<italic>P</italic>
=2.9×10
<sup>−14</sup>
) within
<italic>STXBP5</italic>
. The second locus is on 8p11.21. The lead SNP (rs3136739,
<italic>P</italic>
=1.3×10
<sup>−9</sup>
) is intronic to
<italic>POLB</italic>
and less than 200kb away from the tPA encoding gene
<italic>PLAT</italic>
. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r
<sup>2</sup>
= 0.50) within exon 5 of
<italic>PLAT</italic>
(
<italic>P</italic>
=2.0×10
<sup>−8</sup>
). The third locus is on 12q24.33, with the lead SNP (rs7301826,
<italic>P</italic>
=1.0×10
<sup>−9</sup>
) within intron 7 of
<italic>STX2</italic>
. We further found evidence for association of lead SNPs in
<italic>STXBP5</italic>
and
<italic>STX2</italic>
with expression levels of the respective transcripts. In
<italic>in vitro</italic>
cell studies, silencing
<italic>STXBP5</italic>
decreased release of tPA from vascular endothelial cells, while silencing of
<italic>STX2</italic>
increased tPA release. Through an
<italic>in-silico</italic>
lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke.</p>
</sec>
<sec id="S3">
<title>Conclusions</title>
<p id="P5">We identified three loci associated with circulating tPA levels, the
<italic>PLAT</italic>
region,
<italic>STXBP5</italic>
and
<italic>STX2.</italic>
Our functional studies implicate a novel role for
<italic>STXBP5</italic>
and
<italic>STX2</italic>
in regulating tPA release.</p>
</sec>
</abstract>
<kwd-group>
<kwd>tissue plasminogen activator</kwd>
<kwd>genome-wide association study</kwd>
<kwd>meta-analysis</kwd>
<kwd>cardiovascular disease risk</kwd>
<kwd>fibrinolysis</kwd>
<kwd>hemostasis</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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