Evidence map›Paper›PMID 28209224›Full record

ArticleJournal of the American College of Cardiology2017

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease.

Thomas R Webb, Jeanette Erdmann, Kathleen E Stirrups, Nathan O Stitziel, Nicholas G D Masca, Henning Jansen, Stavroula Kanoni, Christopher P Nelson, Paola G Ferrario, Inke R König and 127 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 9 pooled it
24.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

149 citing papers in PubMed, 9 syntheses or guidelines pooled it, 263 citations in OpenAlex.

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89 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

137 authors at 20 institutions in 12 countries.

Thomas R WebbDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
Jeanette ErdmannInstitute for Cardiogenetics, University of Lübeck, Lübeck, Germany; DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; University Heart Center Luebeck, Lübeck, Germany.
Kathleen E StirrupsWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
Nathan O StitzielCardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri; Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, Missouri.
Nicholas G D MascaDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
Henning JansenDeutsches Herzzentrum München, Technische Universität München, München, Germany; DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
Stavroula KanoniWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
Paola G FerrarioDZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.
Inke R KönigDZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.
John D EicherCenter for Population Studies, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, Massachusetts.
Andrew D JohnsonCenter for Population Studies, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, Massachusetts.
Stephen E HambyDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
Christer BetsholtzDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden; Department of Medical Biochemistry and Biophysics, Vascular Biology Unit, Karolinska Institutet, Stockholm, Sweden.
Arno RuusaleppDepartment of Physiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Tartu, Estonia; Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia; Clinical Gene Networks AB, Stockholm, Sweden.
Oscar FranzénClinical Gene Networks AB, Stockholm, Sweden; Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
Eric E SchadtDepartment of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
Johan L M BjörkegrenDepartment of Medical Biochemistry and Biophysics, Vascular Biology Unit, Karolinska Institutet, Stockholm, Sweden; Department of Physiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Tartu, Estonia; Clinical Gene Networks AB, Stockholm, Sweden; Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
Peter E WeekeDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Laboratory for Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Paul L AuerSchool of Public Heath, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.
Ursula M SchickFred Hutchinson Cancer Research Center, Seattle, Washington; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York.
Yingchang LuThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York.
He ZhangDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan.
Marie-Pierre DubeUniversité de Montréal, Faculté de médecine, Département de médecine, Montreal, Quebec, Canada; Montreal Heart Institute, Montreal, Quebec, Canada.
Anuj GoelDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Martin FarrallDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Gina M PelosoCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Hong-Hee WonCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
Ron DoThe Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York; The Center for Statistical Genetics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Erik van IperenDepartment of Biostatistics, Academic Medical Center, Amsterdam, the Netherlands.
Jochen KruppaInstitute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Robert A ScottMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
Christina WillenborgInstitute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
Peter S BraundDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
Julian C van CapelleveenDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Alex S F DoneyMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Louise A DonnellyMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Rosanna AsseltaDepartment of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Clinical and Research Center, Milan, Italy.
Pier A MerliniNiguarda Hospital, Milan, Italy.
Stefano DugaDepartment of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Clinical and Research Center, Milan, Italy.
Nicola MarzilianoAzienda Sanitaria Locale 3 San Francesco, Nuoro, Italy 3, Nuoro, Italy.
Josh C DennyDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Biomedical informatics, Vanderbilt University Medical Center, Nashville, Tennessee.
Christian ShafferDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Nour Eddine El-MokhtariKlinik für Kardiologie, Pneumologie und Innere Medizin, Imland Klinik Rendsburg, Rendsburg, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Stefanie HeilmannInstitute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Christian HengstenbergMcDonnell Genome Institute, Washington University School of Medicine, Saint Louis, Missouri; Deutsches Herzzentrum München, Technische Universität München, München, Germany.
Per HoffmannInstitute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
Oddgeir L HolmenHUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.
Kristian HveemHUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.
Jan-Håkan JanssonDepartment of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Sweden.
Karl-Heinz JöckelInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
Thorsten KesslerDeutsches Herzzentrum München, Technische Universität München, München, Germany; DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
Jennifer KriebelResearch unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany.
Karl L LaugwitzDZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Eirini MarouliWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Nicola MartinelliDepartment of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy.
Mark I McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Old Road Headington, Oxford, Oxford, United Kingdom.
Natalie R Van ZuydamOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
Christa MeisingerInstitute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, Estonia; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts; Department of Genetics, Harvard Medical School, Boston, Massachusetts; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, Estonia.
Stefan A EscherGenetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Maris AlverEstonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, Tartu, Estonia.
Susanne MoebusInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
Andrew D MorrisSchool of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, Scotland, United Kingdom.
Jarma VirtamoNational Institute for Health and Welfare (THL), Helsinki, Finland.
Majid NikpayRuddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Oliviero OlivieriDepartment of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy.
Sylvie ProvostMontreal Heart Institute, Montreal, Quebec, Canada.
Alaa AlQarawiPrincess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
Neil R RobertsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
Karen O AkinsansyaMerck Sharp & Dohme, Rahway, New Jersey.
Dermot F ReillyMerck Sharp & Dohme, Rahway, New Jersey.
Thomas F VogtMerck Sharp & Dohme, Rahway, New Jersey.
Wu YinMerck Sharp & Dohme, Rahway, New Jersey.
Folkert W AsselbergsDepartment of Cardiology, Division Heart & Lungs, UMC Utrecht, the Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom.
Charles KooperbergFred Hutchinson Cancer Research Center, Seattle, Washington.
Rebecca D JacksonDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Ohio State University, Columbus, Ohio.
Eli StahlDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
Martina Müller-NurasyidDZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Tibor V VargaGenetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Melanie WaldenbergerResearch unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Wellcome Trust Case Control Consortium
Lingyao ZengDeutsches Herzzentrum München, Technische Universität München, München, Germany; DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
Rajiv ChowdhuryMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Veikko SalomaaNational Institute for Health and Welfare (THL), Helsinki, Finland.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden and Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
Philippe AmouyelUniversité de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Lille, France.
Jukka KonttoNational Institute for Health and Welfare (THL), Helsinki, Finland.
MORGAM Investigators
Børge G NordestgaardCopenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jean FerrièresToulouse University School of Medicine, Toulouse, France.
Danish SaleheenDepartment of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Noncommunicable Diseases, Karachi, Pakistan.
Naveed SattarBritish Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Praveen SurendranInstitute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Aline WagnerDepartment of Epîdemiology and Public Health, University of Strasbourg, Strasbourg, France.
Robin YoungMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Joanna M M HowsonMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Adam S ButterworthMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute of Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom.
John DaneshMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute of Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Diego ArdissinoParma University Hospital, Parma, Italy.
Erwin P BottingerThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York.
Raimund ErbelInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
Paul W FranksGenetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden.
Domenico GirelliDepartment of Medicine, Section of Internal Medicine, University of Verona, Verona, Italy.
Alistair S HallLeeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom.
G Kees HovinghDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Adnan KastratiDeutsches Herzzentrum München, Technische Universität München, München, Germany.
Wolfgang LiebInstitute of Epidemiology and Biobank popgen, Christian-Albrechts-University Kiel, Kiel, Germany.
Thomas MeitingerDZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany.
William E KrausDuke Molecular Physiology Institute, Duke University, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina.
Svati H ShahDuke Molecular Physiology Institute, Duke University, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University, Durham, North Carolina.
Ruth McPhersonRuddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Marju Orho-MelanderDepartment of Clinical Sciences in Malmo, Lund University, Clinical Research Center, Malmo, Sweden.
Olle MelanderDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmo, Malmo, Sweden.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, Tartu, Estonia.
Colin N A PalmerMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Annette PetersDZHK, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Daniel J RaderDepartment of Genetics, Cardiovascular Institute and Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Muredach P ReillyDivision of Cardiology, Department of Medicine and the Irving Institute for Clinical and Translational Research, Columbia University, New York, New York.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York; The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York.
Alex P ReinerFred Hutchinson Cancer Research Center, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington.
Dan M RodenDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.
Jean-Claude TardifUniversité de Montréal, Faculté de médecine, Département de médecine, Montreal, Quebec, Canada; Montreal Heart Institute, Montreal, Quebec, Canada.
John R ThompsonNIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
Nicholas J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Cristen J WillerUniversité de Montréal, Faculté de médecine, Département de médecine, Montreal, Quebec, Canada; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom. Electronic address: njs@le.ac.uk.
Heribert SchunkertDeutsches Herzzentrum München, Technische Universität München, München, Germany; DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
Panos DeloukasWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: p.deloukas@qmul.ac.uk.
Sekar KathiresanCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts.
Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators
University of Michigan · USIcahn School of Medicine at Mount Sinai · USNIHR Leicester Cardiovascular Biomedical Research Unit · GBAmsterdam UMC Location University of Amsterdam · NLDeutsches Herzzentrum München · DEFinnish Institute for Health and Welfare · FIFramingham Heart Study · USFred Hutch Cancer Center · USGerman Centre for Cardiovascular Research · DEInstitut für Medizinische Informatik, Biometrie und Epidemiologie · DEMerck & Co., Inc., Rahway, NJ, USA (United States) · USQueen Mary University of London · GBTechnical University of Munich · DEUniversity of Cambridge · GBUniversity of Leicester · GBUniversity of Verona · ITVanderbilt University Medical Center · USHumanitas University · ITLund University · SENational Heart Lung and Blood Institute · US

Funding

Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Using Genetics to Inform Mechanism of Cardiovascular DiseaseR35HL135824 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2017 to 2022
$5.4M
Toward Diagnostics and Therapies of Molecular Subcategories of CADR01HL125863 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BJORKEGREN, JOHAN M · 2015 to 2018
$3.2M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
Rare coding variation and risk for myocardial infarctionK08HL114642 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2012 to 2016
$703k
FHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600k
British Heart Foundation RG/08/014/24067British Heart Foundation RG/14/5/30893British Heart Foundation SP/16/4/32697Medical Research Council MC_PC_13040Medical Research Council MR/K007017/1Medical Research Council MR/L003120/1Medical Research Council MR/M501633/1Medical Research Council MR/M501633/2NHLBI NIH HHS K08 HL114642NHLBI NIH HHS R01 HL125863NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R35 HL135824NIH HHS S10 OD018522NIH HHS S10 OD020069Wellcome Trust
6 · The paper itself

Abstract

backgroundGenome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.

objectivesThis study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.

methodsIn discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.

resultsWe identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10

conclusionsWe identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

Indexed as

Genetic LociGenetic PleiotropyCase-Control StudiesCoronary Artery DiseaseFemaleGene FrequencyGenome-Wide Association StudyHumansMaleOdds RatioPolymorphism, Single Nucleotidecholesteryl ester transfer proteinexpression quantitative trait locigeneticsgenome-wide associationsingle nucleotide polymorphism

Identifiers

PMID28209224
PMCPMC5314135
OpenAlexW2587804655

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