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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation</title><author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name><affiliation><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation></author><author><name sortKey="Sabater Lleal, Maria" sort="Sabater Lleal, Maria" uniqKey="Sabater Lleal M" first="Maria" last="Sabater-Lleal">Maria Sabater-Lleal</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Asselbergs, Folkert W" sort="Asselbergs, Folkert W" uniqKey="Asselbergs F" first="Folkert W." last="Asselbergs">Folkert W. Asselbergs</name><affiliation><nlm:aff id="aff3">Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Tregouet">David Tregouet</name><affiliation><nlm:aff id="aff6">Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></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><nlm:aff id="aff7">Wellcome Trust Sanger Institute, Hinxton, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Ding, Jingzhong" sort="Ding, Jingzhong" uniqKey="Ding J" first="Jingzhong" last="Ding">Jingzhong Ding</name><affiliation><nlm:aff id="aff8">Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation></author><author><name sortKey="Baumert, Jens" sort="Baumert, Jens" uniqKey="Baumert J" first="Jens" last="Baumert">Jens Baumert</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></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><nlm:aff id="aff6">Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Folkersen, Lasse" sort="Folkersen, Lasse" uniqKey="Folkersen L" first="Lasse" last="Folkersen">Lasse Folkersen</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Division of Intramural Research, NHLBI, Bethesda, MD;</nlm:aff></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><nlm:aff id="aff11">Department of Epidemiology, University of Washington, Seattle, WA;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA;</nlm:aff></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><nlm:aff id="aff14">Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Rotterdam Study:</nlm:aff></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><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;</nlm:aff></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><nlm:aff id="aff17">Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Nonprofit LLC, Freiburg, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;</nlm:aff></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><nlm:aff id="aff19">Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></affiliation></author><author><name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name><affiliation><nlm:aff id="aff20">Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Mychaleckyj, Josyf C" sort="Mychaleckyj, Josyf C" uniqKey="Mychaleckyj J" first="Josyf C." last="Mychaleckyj">Josyf C. Mychaleckyj</name><affiliation><nlm:aff id="aff21">Center for Public Health Genomics, University of Virginia, Charlottesville, VA;</nlm:aff></affiliation></author><author><name sortKey="Tang, Weihong" sort="Tang, Weihong" uniqKey="Tang W" first="Weihong" last="Tang">Weihong Tang</name><affiliation><nlm:aff id="aff22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Department of Biostatistics, Boston University, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Sennblad, Bengt" sort="Sennblad, Bengt" uniqKey="Sennblad B" first="Bengt" last="Sennblad">Bengt Sennblad</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff24">Department of Genetics and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH;</nlm:aff></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><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Silbernagel, Gunther" sort="Silbernagel, Gunther" uniqKey="Silbernagel G" first="Günther" last="Silbernagel">Günther Silbernagel</name><affiliation><nlm:aff id="aff27">Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, Eberhard-Karls-University Tübingen, Tübingen, Germany;</nlm:aff></affiliation></author><author><name sortKey="Schrijvers, Elisabeth M C" sort="Schrijvers, Elisabeth M C" uniqKey="Schrijvers E" first="Elisabeth M. C." last="Schrijvers">Elisabeth M. C. Schrijvers</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Smith, Shelly" sort="Smith, Shelly" uniqKey="Smith S" first="Shelly" last="Smith">Shelly Smith</name><affiliation><nlm:aff id="aff28">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation></author><author><name sortKey="Karakas, Mahir" sort="Karakas, Mahir" uniqKey="Karakas M" first="Mahir" last="Karakas">Mahir Karakas</name><affiliation><nlm:aff id="aff29">Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;</nlm:aff></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><nlm:aff id="aff30">Royal North Shore Hospital, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Silveira, Angela" sort="Silveira, Angela" uniqKey="Silveira A" first="Angela" last="Silveira">Angela Silveira</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff31">Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="aff32">Department of Biostatistical Sciences, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></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><nlm:aff id="aff23">Department of Biostatistics, Boston University, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Goel, Anuj" sort="Goel, Anuj" uniqKey="Goel A" first="Anuj" last="Goel">Anuj Goel</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hopewell, Jemma C" sort="Hopewell, Jemma C" uniqKey="Hopewell J" first="Jemma C." last="Hopewell">Jemma C. Hopewell</name><affiliation><nlm:aff id="aff35">Clinical Trial Service Unit, University of Oxford, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C." last="Chambers">John C. Chambers</name><affiliation><nlm:aff id="aff36">Epidemiology and Biostatistics, Imperial College, London, London, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name><affiliation><nlm:aff id="aff38">Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan;</nlm:aff></affiliation><affiliation><nlm:aff id="aff39">Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Lundmark, Per" sort="Lundmark, Per" uniqKey="Lundmark P" first="Per" last="Lundmark">Per Lundmark</name><affiliation><nlm:aff id="aff40">Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;</nlm:aff></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><nlm:aff id="aff41">Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff42">Group Health Research Institute, Group Health Cooperative, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Strawbridge, Rona J" sort="Strawbridge, Rona J" uniqKey="Strawbridge R" first="Rona J." last="Strawbridge">Rona J. Strawbridge</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Boehm, Bernhard O" sort="Boehm, Bernhard O" uniqKey="Boehm B" first="Bernhard O." last="Boehm">Bernhard O. Boehm</name><affiliation><nlm:aff id="aff43">Division of Endocrinology, Diabetes and Metabolism, Graduate School of Molecular Diabetology and Endocrinology, University of Ulm, Ulm, Germany;</nlm:aff></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><nlm:aff id="aff44">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Meisinger, Christa" sort="Meisinger, Christa" uniqKey="Meisinger C" first="Christa" last="Meisinger">Christa Meisinger</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Peden, John F" sort="Peden, John F" uniqKey="Peden J" first="John F." last="Peden">John F. Peden</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff45">Department of Medicine, University of Washington, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name><affiliation><nlm:aff id="aff46">Department of Biostatistics, University of Washington, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Ohrvik, John" sort="Ohrvik, John" uniqKey="Ohrvik J" first="John" last="Öhrvik">John Öhrvik</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Taylor, Kent" sort="Taylor, Kent" uniqKey="Taylor K" first="Kent" last="Taylor">Kent Taylor</name><affiliation><nlm:aff id="aff47">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA;</nlm:aff></affiliation></author><author><name sortKey="Franzosi, Maria Grazia" sort="Franzosi, Maria Grazia" uniqKey="Franzosi M" first="Maria Grazia" last="Franzosi">Maria Grazia Franzosi</name><affiliation><nlm:aff id="aff48">Department of Cardiovascular Research, Istituto Mario Negri, Milano, Italy;</nlm:aff></affiliation></author><author><name sortKey="Seedorf, Udo" sort="Seedorf, Udo" uniqKey="Seedorf U" first="Udo" last="Seedorf">Udo Seedorf</name><affiliation><nlm:aff id="aff49">Gesellschaft für Arterioskleroseforschunge V, Leibniz-Institut für Arterioskleroseforschung an der Universität Münster (LIFA), Münster, Germany;</nlm:aff></affiliation></author><author><name sortKey="Collins, Rory" sort="Collins, Rory" uniqKey="Collins R" first="Rory" last="Collins">Rory Collins</name><affiliation><nlm:aff id="aff35">Clinical Trial Service Unit, University of Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff50">Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Syv Nen, Ann Christine" sort="Syv Nen, Ann Christine" uniqKey="Syv Nen A" first="Ann-Christine" last="Syv Nen">Ann-Christine Syv Nen</name><affiliation><nlm:aff id="aff40">Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;</nlm:aff></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><nlm:aff id="aff51">Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom;</nlm:aff></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><nlm:aff id="aff19">Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></affiliation></author><author><name sortKey="Cushman, Mary" sort="Cushman, Mary" uniqKey="Cushman M" first="Mary" last="Cushman">Mary Cushman</name><affiliation><nlm:aff id="aff52">Departments of Medicine and Pathology, University of Vermont, Burlington, VT; GeneSTAR:</nlm:aff></affiliation><affiliation><nlm:aff id="aff53">Departments of Medicine and Pathology, University of Vermont, Burlington, VT;</nlm:aff></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:aff id="aff54">Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff56">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany;</nlm:aff></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><nlm:aff id="aff22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Basu, Saonli" sort="Basu, Saonli" uniqKey="Basu S" first="Saonli" last="Basu">Saonli Basu</name><affiliation><nlm:aff id="aff57">Division of Biostatistics, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Matijevic, Nena" sort="Matijevic, Nena" uniqKey="Matijevic N" first="Nena" last="Matijevic">Nena Matijevic</name><affiliation><nlm:aff id="aff58">Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, TX; Cardiovascular Health Study:</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S." last="Kooner">Jaspal S. Kooner</name><affiliation><nlm:aff id="aff37">Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><affiliation><nlm:aff id="aff39">Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation><nlm:aff id="aff60">Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff61">General Medicine Division, Massachusetts General Hospital, Boston, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff62">Department of Medicine at Harvard Medical School, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name><affiliation><nlm:aff id="aff63">Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff65">Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA;</nlm:aff></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><nlm:aff id="aff66">Cardiovascular Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;</nlm:aff></affiliation></author><author><name sortKey="Klopp, Norman" sort="Klopp, Norman" uniqKey="Klopp N" first="Norman" last="Klopp">Norman Klopp</name><affiliation><nlm:aff id="aff67">Division of Molecular Epidemiology, Helmholtz Zentrum München, German Resrarch Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="aff68">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD;</nlm:aff></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><nlm:aff id="aff69">Cardiology Team Sachsenhausen, Frankfurt am Main, Germany;</nlm:aff></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><nlm:aff id="aff44">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Watkins, Hugh" sort="Watkins, Hugh" uniqKey="Watkins H" first="Hugh" last="Watkins">Hugh Watkins</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></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><nlm:aff id="aff70">Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></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><nlm:aff id="aff71">Department of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, VT;</nlm:aff></affiliation></author><author><name sortKey="M Rz, Winfried" sort="M Rz, Winfried" uniqKey="M Rz W" first="Winfried" last="M Rz">Winfried M Rz</name><affiliation><nlm:aff id="aff18">Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff72">Synlab Academy, Mannheim, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff73">Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria;</nlm:aff></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><nlm:aff id="aff16">Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name><affiliation><nlm:aff id="aff20">Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></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><nlm:aff id="aff74">Inserm UMR_S 626, Université de la Méditerranée, Marseille, France;</nlm:aff></affiliation></author><author><name sortKey="Koenig, Wolfgang" sort="Koenig, Wolfgang" uniqKey="Koenig W" first="Wolfgang" last="Koenig">Wolfgang Koenig</name><affiliation><nlm:aff id="aff29">Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="aff7">Wellcome Trust Sanger Institute, Hinxton, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="aff75">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff76">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC</nlm:aff></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><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Division of Intramural Research, NHLBI, Bethesda, MD;</nlm:aff></affiliation><affiliation><nlm:aff id="aff77">Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA</nlm:aff></affiliation></author><author><name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22990020</idno><idno type="pmc">3520624</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520624</idno><idno type="RBID">PMC:3520624</idno><idno type="doi">10.1182/blood-2012-06-436188</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">001797</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001797</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation</title><author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name><affiliation><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation></author><author><name sortKey="Sabater Lleal, Maria" sort="Sabater Lleal, Maria" uniqKey="Sabater Lleal M" first="Maria" last="Sabater-Lleal">Maria Sabater-Lleal</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Asselbergs, Folkert W" sort="Asselbergs, Folkert W" uniqKey="Asselbergs F" first="Folkert W." last="Asselbergs">Folkert W. Asselbergs</name><affiliation><nlm:aff id="aff3">Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Tregouet">David Tregouet</name><affiliation><nlm:aff id="aff6">Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></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><nlm:aff id="aff7">Wellcome Trust Sanger Institute, Hinxton, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Ding, Jingzhong" sort="Ding, Jingzhong" uniqKey="Ding J" first="Jingzhong" last="Ding">Jingzhong Ding</name><affiliation><nlm:aff id="aff8">Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation></author><author><name sortKey="Baumert, Jens" sort="Baumert, Jens" uniqKey="Baumert J" first="Jens" last="Baumert">Jens Baumert</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></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><nlm:aff id="aff6">Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Folkersen, Lasse" sort="Folkersen, Lasse" uniqKey="Folkersen L" first="Lasse" last="Folkersen">Lasse Folkersen</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Division of Intramural Research, NHLBI, Bethesda, MD;</nlm:aff></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><nlm:aff id="aff11">Department of Epidemiology, University of Washington, Seattle, WA;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA;</nlm:aff></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><nlm:aff id="aff14">Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Rotterdam Study:</nlm:aff></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><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;</nlm:aff></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><nlm:aff id="aff17">Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Nonprofit LLC, Freiburg, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;</nlm:aff></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><nlm:aff id="aff19">Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></affiliation></author><author><name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name><affiliation><nlm:aff id="aff20">Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Mychaleckyj, Josyf C" sort="Mychaleckyj, Josyf C" uniqKey="Mychaleckyj J" first="Josyf C." last="Mychaleckyj">Josyf C. Mychaleckyj</name><affiliation><nlm:aff id="aff21">Center for Public Health Genomics, University of Virginia, Charlottesville, VA;</nlm:aff></affiliation></author><author><name sortKey="Tang, Weihong" sort="Tang, Weihong" uniqKey="Tang W" first="Weihong" last="Tang">Weihong Tang</name><affiliation><nlm:aff id="aff22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Department of Biostatistics, Boston University, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Sennblad, Bengt" sort="Sennblad, Bengt" uniqKey="Sennblad B" first="Bengt" last="Sennblad">Bengt Sennblad</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff24">Department of Genetics and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH;</nlm:aff></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><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Silbernagel, Gunther" sort="Silbernagel, Gunther" uniqKey="Silbernagel G" first="Günther" last="Silbernagel">Günther Silbernagel</name><affiliation><nlm:aff id="aff27">Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, Eberhard-Karls-University Tübingen, Tübingen, Germany;</nlm:aff></affiliation></author><author><name sortKey="Schrijvers, Elisabeth M C" sort="Schrijvers, Elisabeth M C" uniqKey="Schrijvers E" first="Elisabeth M. C." last="Schrijvers">Elisabeth M. C. Schrijvers</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Smith, Shelly" sort="Smith, Shelly" uniqKey="Smith S" first="Shelly" last="Smith">Shelly Smith</name><affiliation><nlm:aff id="aff28">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation></author><author><name sortKey="Karakas, Mahir" sort="Karakas, Mahir" uniqKey="Karakas M" first="Mahir" last="Karakas">Mahir Karakas</name><affiliation><nlm:aff id="aff29">Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;</nlm:aff></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><nlm:aff id="aff30">Royal North Shore Hospital, University of Sydney, Sydney, Australia;</nlm:aff></affiliation></author><author><name sortKey="Silveira, Angela" sort="Silveira, Angela" uniqKey="Silveira A" first="Angela" last="Silveira">Angela Silveira</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></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><nlm:aff id="aff31">Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Lohman, Kurt" sort="Lohman, Kurt" uniqKey="Lohman K" first="Kurt" last="Lohman">Kurt Lohman</name><affiliation><nlm:aff id="aff32">Department of Biostatistical Sciences, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></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><nlm:aff id="aff23">Department of Biostatistics, Boston University, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Goel, Anuj" sort="Goel, Anuj" uniqKey="Goel A" first="Anuj" last="Goel">Anuj Goel</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hopewell, Jemma C" sort="Hopewell, Jemma C" uniqKey="Hopewell J" first="Jemma C." last="Hopewell">Jemma C. Hopewell</name><affiliation><nlm:aff id="aff35">Clinical Trial Service Unit, University of Oxford, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Chambers, John C" sort="Chambers, John C" uniqKey="Chambers J" first="John C." last="Chambers">John C. Chambers</name><affiliation><nlm:aff id="aff36">Epidemiology and Biostatistics, Imperial College, London, London, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Saleheen, Danish" sort="Saleheen, Danish" uniqKey="Saleheen D" first="Danish" last="Saleheen">Danish Saleheen</name><affiliation><nlm:aff id="aff38">Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan;</nlm:aff></affiliation><affiliation><nlm:aff id="aff39">Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Lundmark, Per" sort="Lundmark, Per" uniqKey="Lundmark P" first="Per" last="Lundmark">Per Lundmark</name><affiliation><nlm:aff id="aff40">Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;</nlm:aff></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><nlm:aff id="aff41">Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff42">Group Health Research Institute, Group Health Cooperative, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Strawbridge, Rona J" sort="Strawbridge, Rona J" uniqKey="Strawbridge R" first="Rona J." last="Strawbridge">Rona J. Strawbridge</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Boehm, Bernhard O" sort="Boehm, Bernhard O" uniqKey="Boehm B" first="Bernhard O." last="Boehm">Bernhard O. Boehm</name><affiliation><nlm:aff id="aff43">Division of Endocrinology, Diabetes and Metabolism, Graduate School of Molecular Diabetology and Endocrinology, University of Ulm, Ulm, Germany;</nlm:aff></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><nlm:aff id="aff44">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Meisinger, Christa" sort="Meisinger, Christa" uniqKey="Meisinger C" first="Christa" last="Meisinger">Christa Meisinger</name><affiliation><nlm:aff id="aff9">Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Peden, John F" sort="Peden, John F" uniqKey="Peden J" first="John F." last="Peden">John F. Peden</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff45">Department of Medicine, University of Washington, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Mcknight, Barbara" sort="Mcknight, Barbara" uniqKey="Mcknight B" first="Barbara" last="Mcknight">Barbara Mcknight</name><affiliation><nlm:aff id="aff46">Department of Biostatistics, University of Washington, Seattle, WA;</nlm:aff></affiliation></author><author><name sortKey="Ohrvik, John" sort="Ohrvik, John" uniqKey="Ohrvik J" first="John" last="Öhrvik">John Öhrvik</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Taylor, Kent" sort="Taylor, Kent" uniqKey="Taylor K" first="Kent" last="Taylor">Kent Taylor</name><affiliation><nlm:aff id="aff47">Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA;</nlm:aff></affiliation></author><author><name sortKey="Franzosi, Maria Grazia" sort="Franzosi, Maria Grazia" uniqKey="Franzosi M" first="Maria Grazia" last="Franzosi">Maria Grazia Franzosi</name><affiliation><nlm:aff id="aff48">Department of Cardiovascular Research, Istituto Mario Negri, Milano, Italy;</nlm:aff></affiliation></author><author><name sortKey="Seedorf, Udo" sort="Seedorf, Udo" uniqKey="Seedorf U" first="Udo" last="Seedorf">Udo Seedorf</name><affiliation><nlm:aff id="aff49">Gesellschaft für Arterioskleroseforschunge V, Leibniz-Institut für Arterioskleroseforschung an der Universität Münster (LIFA), Münster, Germany;</nlm:aff></affiliation></author><author><name sortKey="Collins, Rory" sort="Collins, Rory" uniqKey="Collins R" first="Rory" last="Collins">Rory Collins</name><affiliation><nlm:aff id="aff35">Clinical Trial Service Unit, University of Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff50">Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Syv Nen, Ann Christine" sort="Syv Nen, Ann Christine" uniqKey="Syv Nen A" first="Ann-Christine" last="Syv Nen">Ann-Christine Syv Nen</name><affiliation><nlm:aff id="aff40">Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;</nlm:aff></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><nlm:aff id="aff51">Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom;</nlm:aff></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><nlm:aff id="aff19">Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></affiliation></author><author><name sortKey="Cushman, Mary" sort="Cushman, Mary" uniqKey="Cushman M" first="Mary" last="Cushman">Mary Cushman</name><affiliation><nlm:aff id="aff52">Departments of Medicine and Pathology, University of Vermont, Burlington, VT; GeneSTAR:</nlm:aff></affiliation><affiliation><nlm:aff id="aff53">Departments of Medicine and Pathology, University of Vermont, Burlington, VT;</nlm:aff></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:aff id="aff54">Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff56">Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany;</nlm:aff></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><nlm:aff id="aff22">Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Basu, Saonli" sort="Basu, Saonli" uniqKey="Basu S" first="Saonli" last="Basu">Saonli Basu</name><affiliation><nlm:aff id="aff57">Division of Biostatistics, University of Minnesota, Minneapolis, MN;</nlm:aff></affiliation></author><author><name sortKey="Matijevic, Nena" sort="Matijevic, Nena" uniqKey="Matijevic N" first="Nena" last="Matijevic">Nena Matijevic</name><affiliation><nlm:aff id="aff58">Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, TX; Cardiovascular Health Study:</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Kooner, Jaspal S" sort="Kooner, Jaspal S" uniqKey="Kooner J" first="Jaspal S." last="Kooner">Jaspal S. Kooner</name><affiliation><nlm:aff id="aff37">Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="aff15">Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><affiliation><nlm:aff id="aff39">Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Clarke, Robert" sort="Clarke, Robert" uniqKey="Clarke R" first="Robert" last="Clarke">Robert Clarke</name><affiliation><nlm:aff id="aff60">Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff61">General Medicine Division, Massachusetts General Hospital, Boston, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff62">Department of Medicine at Harvard Medical School, Boston, MA;</nlm:aff></affiliation></author><author><name sortKey="Kathiresan, Sekar" sort="Kathiresan, Sekar" uniqKey="Kathiresan S" first="Sekar" last="Kathiresan">Sekar Kathiresan</name><affiliation><nlm:aff id="aff63">Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA;</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff id="aff65">Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA;</nlm:aff></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><nlm:aff id="aff66">Cardiovascular Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;</nlm:aff></affiliation></author><author><name sortKey="Klopp, Norman" sort="Klopp, Norman" uniqKey="Klopp N" first="Norman" last="Klopp">Norman Klopp</name><affiliation><nlm:aff id="aff67">Division of Molecular Epidemiology, Helmholtz Zentrum München, German Resrarch Center for Environmental Health, Neuherberg, Germany;</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="aff68">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD;</nlm:aff></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><nlm:aff id="aff69">Cardiology Team Sachsenhausen, Frankfurt am Main, Germany;</nlm:aff></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><nlm:aff id="aff44">Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Watkins, Hugh" sort="Watkins, Hugh" uniqKey="Watkins H" first="Hugh" last="Watkins">Hugh Watkins</name><affiliation><nlm:aff id="aff33">Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff34">Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</nlm:aff></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><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></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><nlm:aff id="aff70">Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD;</nlm:aff></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><nlm:aff id="aff71">Department of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, VT;</nlm:aff></affiliation></author><author><name sortKey="M Rz, Winfried" sort="M Rz, Winfried" uniqKey="M Rz W" first="Winfried" last="M Rz">Winfried M Rz</name><affiliation><nlm:aff id="aff18">Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff72">Synlab Academy, Mannheim, Germany;</nlm:aff></affiliation><affiliation><nlm:aff id="aff73">Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria;</nlm:aff></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><nlm:aff id="aff16">Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name><affiliation><nlm:aff id="aff20">Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</nlm:aff></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><nlm:aff id="aff74">Inserm UMR_S 626, Université de la Méditerranée, Marseille, France;</nlm:aff></affiliation></author><author><name sortKey="Koenig, Wolfgang" sort="Koenig, Wolfgang" uniqKey="Koenig W" first="Wolfgang" last="Koenig">Wolfgang Koenig</name><affiliation><nlm:aff id="aff29">Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="aff7">Wellcome Trust Sanger Institute, Hinxton, United Kingdom;</nlm:aff></affiliation><affiliation><nlm:aff id="aff25">Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</nlm:aff></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><nlm:aff id="aff59">Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</nlm:aff></affiliation></author><author><name sortKey="Liu, Yongmei" sort="Liu, Yongmei" uniqKey="Liu Y" first="Yongmei" last="Liu">Yongmei Liu</name><affiliation><nlm:aff id="aff75">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff76">Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC</nlm:aff></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><nlm:aff id="aff1">National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Division of Intramural Research, NHLBI, Bethesda, MD;</nlm:aff></affiliation><affiliation><nlm:aff id="aff77">Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA</nlm:aff></affiliation></author><author><name sortKey="Hamsten, Anders" sort="Hamsten, Anders" uniqKey="Hamsten A" first="Anders" last="Hamsten">Anders Hamsten</name><affiliation><nlm:aff id="aff2">Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</nlm:aff></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (<italic>P</italic> < 5 × 10<sup>−8</sup>) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of <italic>SERPINE1</italic> (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to <italic>SERPINE1</italic> (rs6976053, discovery <italic>P</italic> = 3.4 × 10<sup>−10</sup>); chromosome 11p15.2 within <italic>ARNTL</italic> (rs6486122, discovery <italic>P</italic> = 3.0 × 10<sup>−8</sup>); and chromosome 3p25.2 within <italic>PPARG</italic> (rs11128603, discovery <italic>P</italic> = 2.9 × 10<sup>−8</sup>). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at <italic>ARNTL</italic> (<italic>P</italic> < .05). Functional studies identified <italic>MUC3</italic> as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in <italic>SERPINE1</italic> and <italic>ARNTL</italic> and an SNP associated with the expression of <italic>MUC3</italic> were robustly associated with circulating levels of PAI-1.</p></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>
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contrib-type="author"><name><surname>Cambien</surname><given-names>Francois</given-names></name><xref ref-type="aff" rid="aff20">20</xref></contrib><contrib contrib-type="author"><collab>CARDIOGENICS Consortium</collab></contrib><contrib contrib-type="author"><name><surname>Morange</surname><given-names>Pierre-Emmanuel</given-names></name><xref ref-type="aff" rid="aff74">74</xref></contrib><contrib contrib-type="author"><name><surname>Koenig</surname><given-names>Wolfgang</given-names></name><xref ref-type="aff" rid="aff29">29</xref></contrib><contrib contrib-type="author"><name><surname>Soranzo</surname><given-names>Nicole</given-names></name><xref ref-type="aff" rid="aff7">7</xref><xref ref-type="aff" rid="aff25">25</xref></contrib><contrib contrib-type="author"><name><surname>van der Harst</surname><given-names>Pim</given-names></name><xref ref-type="aff" rid="aff59">59</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yongmei</given-names></name><xref ref-type="aff" rid="aff75">75</xref><xref ref-type="aff" rid="aff76">76</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>O'Donnell</surname><given-names>Christopher J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff10">10</xref><xref ref-type="aff" rid="aff77">77</xref><xref ref-type="author-notes" rid="FN2">†</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Hamsten</surname><given-names>Anders</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="author-notes" rid="FN2">†</xref></contrib><aff id="aff1"><label>1</label>National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;</aff><aff id="aff2"><label>2</label>Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;</aff><aff id="aff3"><label>3</label>Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands;</aff><aff id="aff4"><label>4</label>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;</aff><aff id="aff5"><label>5</label>Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands;</aff><aff id="aff6"><label>6</label>Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</aff><aff id="aff7"><label>7</label>Wellcome Trust Sanger Institute, Hinxton, United Kingdom;</aff><aff id="aff8"><label>8</label>Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC;</aff><aff id="aff9"><label>9</label>Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</aff><aff id="aff10"><label>10</label>Division of Intramural Research, NHLBI, Bethesda, MD;</aff><aff id="aff11"><label>11</label>Department of Epidemiology, University of Washington, Seattle, WA;</aff><aff id="aff12"><label>12</label>Group Health Research Institute, Group Health Cooperative, Seattle, WA;</aff><aff id="aff13"><label>13</label>Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA;</aff><aff id="aff14"><label>14</label>Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Rotterdam Study:</aff><aff id="aff15"><label>15</label>Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;</aff><aff id="aff16"><label>16</label>Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;</aff><aff id="aff17"><label>17</label>Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Nonprofit LLC, Freiburg, Germany;</aff><aff id="aff18"><label>18</label>Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;</aff><aff id="aff19"><label>19</label>Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;</aff><aff id="aff20"><label>20</label>Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;</aff><aff id="aff21"><label>21</label>Center for Public Health Genomics, University of Virginia, Charlottesville, VA;</aff><aff id="aff22"><label>22</label>Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;</aff><aff id="aff23"><label>23</label>Department of Biostatistics, Boston University, Boston, MA;</aff><aff id="aff24"><label>24</label>Department of Genetics and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH;</aff><aff id="aff25"><label>25</label>Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;</aff><aff id="aff26"><label>26</label>Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;</aff><aff id="aff27"><label>27</label>Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, Eberhard-Karls-University Tübingen, Tübingen, Germany;</aff><aff id="aff28"><label>28</label>Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</aff><aff id="aff29"><label>29</label>Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;</aff><aff id="aff30"><label>30</label>Royal North Shore Hospital, University of Sydney, Sydney, Australia;</aff><aff id="aff31"><label>31</label>Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</aff><aff id="aff32"><label>32</label>Department of Biostatistical Sciences, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</aff><aff id="aff33"><label>33</label>Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;</aff><aff id="aff34"><label>34</label>Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;</aff><aff id="aff35"><label>35</label>Clinical Trial Service Unit, University of Oxford, United Kingdom;</aff><aff id="aff36"><label>36</label>Epidemiology and Biostatistics, Imperial College, London, London, United Kingdom;</aff><aff id="aff37"><label>37</label>Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;</aff><aff id="aff38"><label>38</label>Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan;</aff><aff id="aff39"><label>39</label>Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;</aff><aff id="aff40"><label>40</label>Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;</aff><aff id="aff41"><label>41</label>Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA;</aff><aff id="aff42"><label>42</label>Group Health Research Institute, Group Health Cooperative, Seattle, WA;</aff><aff id="aff43"><label>43</label>Division of Endocrinology, Diabetes and Metabolism, Graduate School of Molecular Diabetology and Endocrinology, University of Ulm, Ulm, Germany;</aff><aff id="aff44"><label>44</label>Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;</aff><aff id="aff45"><label>45</label>Department of Medicine, University of Washington, Seattle, WA;</aff><aff id="aff46"><label>46</label>Department of Biostatistics, University of Washington, Seattle, WA;</aff><aff id="aff47"><label>47</label>Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA;</aff><aff id="aff48"><label>48</label>Department of Cardiovascular Research, Istituto Mario Negri, Milano, Italy;</aff><aff id="aff49"><label>49</label>Gesellschaft für Arterioskleroseforschunge V, Leibniz-Institut für Arterioskleroseforschung an der Universität Münster (LIFA), Münster, Germany;</aff><aff id="aff50"><label>50</label>Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;</aff><aff id="aff51"><label>51</label>Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom;</aff><aff id="aff52"><label>52</label>Departments of Medicine and Pathology, University of Vermont, Burlington, VT; GeneSTAR:</aff><aff id="aff53"><label>53</label>Departments of Medicine and Pathology, University of Vermont, Burlington, VT;</aff><aff id="aff54"><label>54</label>Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;</aff><aff id="aff55"><label>55</label>Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology and Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany;</aff><aff id="aff56"><label>56</label>Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany;</aff><aff id="aff57"><label>57</label>Division of Biostatistics, University of Minnesota, Minneapolis, MN;</aff><aff id="aff58"><label>58</label>Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, TX; Cardiovascular Health Study:</aff><aff id="aff59"><label>59</label>Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;</aff><aff id="aff60"><label>60</label>Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;</aff><aff id="aff61"><label>61</label>General Medicine Division, Massachusetts General Hospital, Boston, MA;</aff><aff id="aff62"><label>62</label>Department of Medicine at Harvard Medical School, Boston, MA;</aff><aff id="aff63"><label>63</label>Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA;</aff><aff id="aff64"><label>64</label>Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA;</aff><aff id="aff65"><label>65</label>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA;</aff><aff id="aff66"><label>66</label>Cardiovascular Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;</aff><aff id="aff67"><label>67</label>Division of Molecular Epidemiology, Helmholtz Zentrum München, German Resrarch Center for Environmental Health, Neuherberg, Germany;</aff><aff id="aff68"><label>68</label>Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD;</aff><aff id="aff69"><label>69</label>Cardiology Team Sachsenhausen, Frankfurt am Main, Germany;</aff><aff id="aff70"><label>70</label>Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD;</aff><aff id="aff71"><label>71</label>Department of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, VT;</aff><aff id="aff72"><label>72</label>Synlab Academy, Mannheim, Germany;</aff><aff id="aff73"><label>73</label>Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria;</aff><aff id="aff74"><label>74</label>Inserm UMR_S 626, Université de la Méditerranée, Marseille, France;</aff><aff id="aff75"><label>75</label>Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;</aff><aff id="aff76"><label>76</label>Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; and</aff><aff id="aff77"><label>77</label>Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA</aff></contrib-group><author-notes><fn fn-type="equal" id="FN1"><label>*</label><p>J.H. and M.S.-L. contributed equally to this work.</p></fn><fn fn-type="equal" id="FN2"><label>†</label><p>C.J.O. and A.H. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>6</day><month>12</month><year>2012</year></pub-date><pub-date pub-type="epreprint"><day>18</day><month>9</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>6</day><month>12</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>120</volume><issue>24</issue><fpage>4873</fpage><lpage>4881</lpage><history><date date-type="received"><day>11</day><month>6</month><year>2012</year></date><date date-type="accepted"><day>14</day><month>8</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by The American Society of Hematology</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh805012004873.pdf"></self-uri><abstract><p>We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (<italic>P</italic> < 5 × 10<sup>−8</sup>) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of <italic>SERPINE1</italic> (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to <italic>SERPINE1</italic> (rs6976053, discovery <italic>P</italic> = 3.4 × 10<sup>−10</sup>); chromosome 11p15.2 within <italic>ARNTL</italic> (rs6486122, discovery <italic>P</italic> = 3.0 × 10<sup>−8</sup>); and chromosome 3p25.2 within <italic>PPARG</italic> (rs11128603, discovery <italic>P</italic> = 2.9 × 10<sup>−8</sup>). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at <italic>ARNTL</italic> (<italic>P</italic> < .05). Functional studies identified <italic>MUC3</italic> as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in <italic>SERPINE1</italic> and <italic>ARNTL</italic> and an SNP associated with the expression of <italic>MUC3</italic> were robustly associated with circulating levels of PAI-1.</p></abstract><funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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