Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

Stitziel, Nathan O. (author): Washington University in St. Louis,University of Verona

Stirrups, Kathleen E. (author): University of Cambridge

Masca, Nicholas G. D. (author): Glenfield Hospital,University of Verona

Erdmann, Jeanette (author): German Centre for Cardiovascular Research

Ferrario, Paola G. (author): British Columbia Children's Hospital

Koenig, Inke R. (author): British Columbia Children's Hospital

Weeke, Peter E. (author): Copenhagen University Hospital

Webb, Thomas R. (author): Glenfield Hospital

Auer, Paul L. (author): University of Wisconsin-Milwaukee

Schick, Ursula M. (author): Icahn School of Medicine at Mount Sinai

Lu, Yingchang (author): Icahn School of Medicine at Mount Sinai

Zhang, He (author): University of Michigan

Dube, Marie-Pierre (author): Montreal Heart Institute

Goel, Anuj (author): University of Oxford

Farrall, Martin (author): University of Oxford

Peloso, Gina M. (author): Helsinki University Central Hospital

Won, Hong-Hee (author): Sungkyunkwan University

Do, Ron (author): Icahn School of Medicine at Mount Sinai

van Iperen, Erik (author): Academic Medical Center of University of Amsterdam (AMC)

Kanoni, Stavroula (author): Queen Mary University

Kruppa, Jochen (author): University of Göttingen

Mahajan, Anubha (author): University of Oxford

Scott, Robert A. (author): Addenbrooke's Hospital,King Abdulaziz University

Willenborg, Christina (author): German Centre for Cardiovascular Research

Braund, Peter S. (author): Glenfield Hospital

van Capelleveen, Julian C. (author): Academic Medical Center of University of Amsterdam (AMC)

Doney, Alex S. F. (author): University of Dundee

Donnelly, Louise A. (author): University of Dundee

Asselta, Rosanna (author): Humanitas Research Hospital

Merlini, Piera A. (author): Niguarda Hospital

Duga, Stefano (author): Humanitas Research Hospital

Marziliano, Nicola (author): Associazione per lo Studio della Trombosi in Cardiologia

Denny, Josh C. (author): Vanderbilt University

Shaffer, Christian M. (author): Vanderbilt University,Helmholtz Zentrum München

El-Mokhtari, Nour Eddine (author): Kreiskrankenhaus Rendsburg

Franke, Andre (author): University of Kiel

Gottesman, Omri (author): Icahn School of Medicine at Mount Sinai

Heilmann, Stefanie (author): University of Bonn

Hengstenberg, Christian (author): Technical University of Munich

Hoffmann, Per (author): University of Basel

Holmen, Oddgeir L. (author): St. Olav’s University Hospital

Hveem, Kristian (author): Nord-Trøndelag Health Trust

Jansson, Jan-Håkan (author): Umeå University,Umeå universitet,Medicin

Joeckel, Karl-Heinz (author): University Hospital Essen

Kessler, Thorsten (author): Technical University of Munich

Kriebel, Jennifer (author): German Center for Diabetes Research

Laugwitz, Karl L. (author): Klinikum rechts der Isar

Marouli, Eirini (author): Queen Mary University

Martinelli, Nicola (author): University of Verona

McCarthy, Mark I. (author): Churchill Hospital

Van Zuydam, Natalie R. (author): University of Oxford

Meisinger, Christa (author)

Esko, Tonu (author): University of Tartu

Mihailov, Evelin (author): University of Tartu

Andersson Escher, Stefan (author): Lund University

Alver, Maris (author): University of Tartu

Moebus, Susanne (author): University Hospital Essen

Morris, Andrew D. (author): University of Edinburgh

Mueller-Nurasyid, Martina (author): Helmholtz Zentrum München

Nikpay, Majid (author): University of Ottawa

Olivieri, Oliviero (author): Merck Sharp And Dohme Corp., US

Perreault, Louis-Philippe Lemieux (author): Montreal Heart Institute

AlQarawi, Alaa (author): University of Dundee

Robertson, Neil R. (author): University of Oxford

Akinsanya, Karen O. (author)

Reilly, Dermot F. (author): Merck Sharp And Dohme Corp., US

Vogt, Thomas F. (author): Merck Sharp And Dohme Corp., US

Yin, Wu (author): Merck Sharp And Dohme Corp., US

Asselbergs, Folkert W. (author): University Medical Center Utrecht

Kooperberg, Charles (author): University of Washington

Jackson, Rebecca D. (author): Ohio State University

Stahl, Eli (author): Icahn School of Medicine at Mount Sinai

Strauch, Konstantin (author): Helmholtz Zentrum München

Varga, Tibor V. (author): Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups

Waldenberger, Melanie (author): Helmholtz Zentrum München

Zeng, Lingyao (author): Technical University of Munich

Kraja, Aldi T. (author): Washington University in St. Louis

Liu, Chunyu (author): National Heart Lung and Blood Institute

Ehret, Georg B. (author): Johns Hopkins University

Newton-Cheh, Christopher (author): Helsinki University Central Hospital

Chasman, Daniel I. (author): Brigham and Women's Hospital / Harvard Medical School

Chowdhury, Rajiv (author): University of Cambridge

Ferrario, Marco (author): University of Insubria

Ford, Ian (author): University of Glasgow

Jukema, J. Wouter (author): Leiden University Medical Centre

Kee, Frank (author): Queen's University Belfast

Kuulasmaa, Kari (author): Finnish National Institute for Health and Welfare

Nordestgaard, Borge G. (author): Copenhagen University Hospital

Perola, Markus (author): Finnish National Institute for Health and Welfare

Saleheen, Danish (author): Center for Non-Communicable Diseases

Sattar, Naveed (author): University of Glasgow

Surendran, Praveen (author): University of Cambridge

Tregouet, David (author): Pitié-Salpêtrière University Hospital

Young, Robin (author): University of Cambridge

Howson, Joanna M. M. (author): University of Cambridge

Butterworth, Adam S. (author): University of Cambridge

Danesh, John (author): Wellcome Trust Sanger Institute

Ardissino, Diego (author): Associazione per lo Studio della Trombosi in Cardiologia

Bottinger, Erwin P. (author): Icahn School of Medicine at Mount Sinai

Erbel, Raimund (author): University Hospital Essen

Franks, Paul W. (author): Umeå University,Lund University,Lunds universitet,Livsmedelsteknik,Avdelningen för livsmedel och läkemedel,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Department of Food Technology, Engineering and Nutrition,Division of Food and Pharma,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH,Genetic and Molecular Epidemiology,Lund University Research Groups,Harvard University,Norrland University Hospital

Girelli, Domenico (author)

Hall, Alistair S. (author): University of Leeds

Hovingh, G. Kees (author): Academic Medical Center of University of Amsterdam (AMC)

Kastrati, Adnan (author): Technical University of Munich

Lieb, Wolfgang (author): University of Kiel

Meitinger, Thomas (author): Helmholtz Zentrum München

Kraus, William E. (author): Duke University

Shah, Svati H. (author): Duke University

McPherson, Ruth (author): University of Ottawa

Orho-Melander, Marju (author): Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups

Melander, Olle (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Cardiovascular Research - Hypertension,Lund University Research Groups

Metspalu, Andres (author): University of Tartu

Palmer, Colin N. A. (author)

Peters, Annette (author): Helmholtz Zentrum München

Rader, Daniel J. (author): University of Pennsylvania

Reilly, Muredach P. (author): University of Pennsylvania

Loos, Ruth J. F. (author): Icahn School of Medicine at Mount Sinai

Reiner, Alex P. (author): University of Washington

Roden, Dan M. (author): Vanderbilt University

Tardif, Jean-Claude (author): Montreal Heart Institute

Thompson, John R. (author): Glenfield Hospital

Wareham, Nicholas J. (author): Addenbrooke's Hospital

Watkins, Hugh (author): University of Oxford

Willer, Cristen J. (author): University of Michigan

Kathiresan, Sekar (author): Helsinki University Central Hospital

Deloukas, Panos (author): King Abdulaziz University

Samani, Nilesh J. (author): Glenfield Hospital

Schunkert, Heribert (author): Technical University of Munich

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Washington University in St Louis University of Verona (creator_code:org_t)

2016
2016
English.
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144

Related links:: http://dx.doi.org/10...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.

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By the author/editor: Stitziel, Nathan ...; Stirrups, Kathle ...; Masca, Nicholas ...; Erdmann, Jeanett ...; Ferrario, Paola ...; Koenig, Inke R.; show more...; Weeke, Peter E.; Webb, Thomas R.; Auer, Paul L.; Schick, Ursula M ...; Lu, Yingchang; Zhang, He; Dube, Marie-Pier ...; Goel, Anuj; Farrall, Martin; Peloso, Gina M.; Won, Hong-Hee; Do, Ron; van Iperen, Erik; Kanoni, Stavroul ...; Kruppa, Jochen; Mahajan, Anubha; Scott, Robert A.; Willenborg, Chri ...; Braund, Peter S.; van Capelleveen, ...; Doney, Alex S. F ...; Donnelly, Louise ...; Asselta, Rosanna; Merlini, Piera A ...; Duga, Stefano; Marziliano, Nico ...; Denny, Josh C.; Shaffer, Christi ...; El-Mokhtari, Nou ...; Franke, Andre; Gottesman, Omri; Heilmann, Stefan ...; Hengstenberg, Ch ...; Hoffmann, Per; Holmen, Oddgeir ...; Hveem, Kristian; Jansson, Jan-Håk ...; Joeckel, Karl-He ...; Kessler, Thorste ...; Kriebel, Jennife ...; Laugwitz, Karl L ...; Marouli, Eirini; Martinelli, Nico ...; McCarthy, Mark I ...; Van Zuydam, Nata ...; Meisinger, Chris ...; Esko, Tonu; Mihailov, Evelin; Andersson Escher ...; Alver, Maris; Moebus, Susanne; Morris, Andrew D ...; Mueller-Nurasyid ...; Nikpay, Majid; Olivieri, Olivie ...; Perreault, Louis ...; AlQarawi, Alaa; Robertson, Neil ...; Akinsanya, Karen ...; Reilly, Dermot F ...; Vogt, Thomas F.; Yin, Wu; Asselbergs, Folk ...; Kooperberg, Char ...; Jackson, Rebecca ...; Stahl, Eli; Strauch, Konstan ...; Varga, Tibor V.; Waldenberger, Me ...; Zeng, Lingyao; Kraja, Aldi T.; Liu, Chunyu; Ehret, Georg B.; Newton-Cheh, Chr ...; Chasman, Daniel ...; Chowdhury, Rajiv; Ferrario, Marco; Ford, Ian; Jukema, J. Woute ...; Kee, Frank; Kuulasmaa, Kari; Nordestgaard, Bo ...; Perola, Markus; Saleheen, Danish; Sattar, Naveed; Surendran, Prave ...; Tregouet, David; Young, Robin; Howson, Joanna M ...; Butterworth, Ada ...; Danesh, John; Ardissino, Diego; Bottinger, Erwin ...; Erbel, Raimund; Franks, Paul W.; Girelli, Domenic ...; Hall, Alistair S ...; Hovingh, G. Kees; Kastrati, Adnan; Lieb, Wolfgang; Meitinger, Thoma ...; Kraus, William E ...; Shah, Svati H.; McPherson, Ruth; Orho-Melander, M ...; Melander, Olle; Metspalu, Andres; Palmer, Colin N. ...; Peters, Annette; Rader, Daniel J.; Reilly, Muredach ...; Loos, Ruth J. F.; Reiner, Alex P.; Roden, Dan M.; Tardif, Jean-Cla ...; Thompson, John R ...; Wareham, Nichola ...; Watkins, Hugh; Willer, Cristen ...; Kathiresan, Seka ...; Deloukas, Panos; Samani, Nilesh J ...; Schunkert, Herib ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: New England Jour ...

By the university: Umeå University; Lund University

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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

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