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Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction

Author

Listed:
  • Ron Do

    (Center for Human Genetic Research, Massachusetts General Hospital
    Cardiovascular Research Center, Massachusetts General Hospital
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Nathan O. Stitziel

    (Washington University School of Medicine, St Louis, Missouri 63110, USA.
    Washington University School of Medicine)

  • Hong-Hee Won

    (Center for Human Genetic Research, Massachusetts General Hospital
    Cardiovascular Research Center, Massachusetts General Hospital
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Anders Berg Jørgensen

    (Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen)

  • Stefano Duga

    (Università degli Studi di Milano)

  • Pier Angelica Merlini

    (Ospedale Niguarda)

  • Adam Kiezun

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Martin Farrall

    (The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK.)

  • Anuj Goel

    (The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK.)

  • Or Zuk

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Illaria Guella

    (Università degli Studi di Milano)

  • Rosanna Asselta

    (Università degli Studi di Milano)

  • Leslie A. Lange

    (University of North Carolina)

  • Gina M. Peloso

    (Center for Human Genetic Research, Massachusetts General Hospital
    Cardiovascular Research Center, Massachusetts General Hospital
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Paul L. Auer

    (Fred Hutchinson Cancer Research Center)

  • Domenico Girelli

    (University of Verona School of Medicine, Verona 37129, Italy.)

  • Nicola Martinelli

    (University of Verona School of Medicine, Verona 37129, Italy.)

  • Deborah N. Farlow

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Mark A. DePristo

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Robert Roberts

    (John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.)

  • Alexander F. R. Stewart

    (John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.)

  • Danish Saleheen

    (University of Cambridge, Cambridge CB2 1TN, UK.)

  • John Danesh

    (University of Cambridge, Cambridge CB2 1TN, UK.)

  • Stephen E. Epstein

    (MedStar Health Research Institute, Cardiovascular Research Institute)

  • Suthesh Sivapalaratnam

    (Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.)

  • G. Kees Hovingh

    (Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.)

  • John J. Kastelein

    (Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.)

  • Nilesh J. Samani

    (University of Leicester, and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK.)

  • Heribert Schunkert

    (DZHK (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Deutsches Herzzentrum München, Technische Universität München, Berlin 13347, Germany.)

  • Jeanette Erdmann

    (Medizinische Klinik II, University of Lübeck, Lübeck 23562, Germany.)

  • Svati H. Shah

    (Center for Human Genetics, Duke University
    Duke University School of Medicine)

  • William E. Kraus

    (Duke University School of Medicine)

  • Robert Davies

    (University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.)

  • Majid Nikpay

    (University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.)

  • Christopher T. Johansen

    (Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.)

  • Jian Wang

    (Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.)

  • Robert A. Hegele

    (Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.
    Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.)

  • Eliana Hechter

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Winfried Marz

    (Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany.
    Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.
    Synlab Academy, Mannheim 68259, Germany.)

  • Marcus E. Kleber

    (Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany.)

  • Jie Huang

    (The National Heart, Lung, Blood Institute’s Framingham Heart Study)

  • Andrew D. Johnson

    (National Heart, Lung, and Blood Institute Center for Population Studies, The Framingham Heart Study)

  • Mingyao Li

    (School of Medicine, University of Pennsylvania)

  • Greg L. Burke

    (University of Alabama–Birmingham)

  • Myron Gross

    (School of Medicine, University of Minnesota)

  • Yongmei Liu

    (School of Medicine, Wake Forest University)

  • Themistocles L. Assimes

    (Stanford University School of Medicine)

  • Gerardo Heiss

    (University of North Carolina)

  • Ethan M. Lange

    (University of North Carolina
    Carolina Center for Genome Sciences, University of North Carolina)

  • Aaron R. Folsom

    (University of Minnesota School of Public Health)

  • Herman A. Taylor

    (University of Mississippi Medical Center)

  • Oliviero Olivieri

    (University of Verona School of Medicine, Verona 37129, Italy.)

  • Anders Hamsten

    (Atherosclerosis Research Unit, and Center for Molecular Medicine, Karolinska Institutet, Stockholm 171 77, Sweden.)

  • Robert Clarke

    (Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX1 2JD, UK.)

  • Dermot F. Reilly

    (Merck Sharp & Dohme Corporation)

  • Wu Yin

    (Merck Sharp & Dohme Corporation)

  • Manuel A. Rivas

    (The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK.)

  • Peter Donnelly

    (The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK.
    University of Oxford, Oxford OX1 2JD, UK.)

  • Jacques E. Rossouw

    (National Heart, Lung, and Blood Institute)

  • Bruce M. Psaty

    (Cardiovascular Health Research Unit, Epidemiology, and Health Services, University of Washington
    Group Health Research Institute, Group Health Cooperative)

  • David M. Herrington

    (Section on Cardiology, and Public Health Sciences, Wake Forest School of Medicine, Winston–Salem, North Carolina 27106, USA.)

  • James G. Wilson

    (Jackson Heart Study, University of Mississippi Medical Center, Jackson State University, Jackson, Mississippi 39217, USA.)

  • Stephen S. Rich

    (Center for Public Health Genomics, University of Virginia)

  • Michael J. Bamshad

    (University of Washington
    Seattle Children’s Hospital
    University of Washington)

  • Russell P. Tracy

    (University of Vermont)

  • L. Adrienne Cupples

    (Boston University School of Public Health)

  • Daniel J. Rader

    (Perelman School of Medicine, University of Pennsylvania)

  • Muredach P. Reilly

    (Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania)

  • John A. Spertus

    (St Luke’s Mid America Heart Institute, University of Missouri-Kansas City)

  • Sharon Cresci

    (Washington University School of Medicine, St Louis, Missouri 63110, USA.
    Washington University in St Louis)

  • Jaana Hartiala

    (University of Southern California Keck School of Medicine)

  • W. H. Wilson Tang

    (Cardiovascular Medicine, Cleveland Clinic)

  • Stanley L. Hazen

    (Cardiovascular Medicine, Cleveland Clinic)

  • Hooman Allayee

    (University of Southern California Keck School of Medicine)

  • Alex P. Reiner

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • Christopher S. Carlson

    (Fred Hutchinson Cancer Research Center)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Rebecca D. Jackson

    (Ohio State University)

  • Eric Boerwinkle

    (Human Genetics Center, The University of Texas Health Science Center at Houston)

  • Eric S. Lander

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Stephen M. Schwartz

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • David S. Siscovick

    (University of Washington
    School of Medicine, University of Washington)

  • Ruth McPherson

    (University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.)

  • Anne Tybjaerg-Hansen

    (Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen
    Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 København N, Denmark.)

  • Goncalo R. Abecasis

    (Center for Statistical Genetics, University of Michigan, Ann Arbor, Missouri 48109, USA.)

  • Hugh Watkins

    (The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK.
    The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK.)

  • Deborah A. Nickerson

    (University of Washington)

  • Diego Ardissino

    (Parma Hospital, Parma 43100, Italy.)

  • Shamil R. Sunyaev

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center
    Brigham and Women’s Hospital, Harvard Medical School)

  • Christopher J. O'Donnell

    (The National Heart, Lung, Blood Institute’s Framingham Heart Study)

  • David Altshuler

    (Center for Human Genetic Research, Massachusetts General Hospital
    Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Stacey Gabriel

    (Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

  • Sekar Kathiresan

    (Center for Human Genetic Research, Massachusetts General Hospital
    Cardiovascular Research Center, Massachusetts General Hospital
    Harvard Medical School
    Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center)

Abstract

Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins.

Suggested Citation

  • Ron Do & Nathan O. Stitziel & Hong-Hee Won & Anders Berg Jørgensen & Stefano Duga & Pier Angelica Merlini & Adam Kiezun & Martin Farrall & Anuj Goel & Or Zuk & Illaria Guella & Rosanna Asselta & Lesli, 2015. "Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction," Nature, Nature, vol. 518(7537), pages 102-106, February.
  • Handle: RePEc:nat:nature:v:518:y:2015:i:7537:d:10.1038_nature13917
    DOI: 10.1038/nature13917
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    Citations

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    Cited by:

    1. Young Jin Kim & Sanghoon Moon & Mi Yeong Hwang & Sohee Han & Hye-Mi Jang & Jinhwa Kong & Dong Mun Shin & Kyungheon Yoon & Sung Min Kim & Jong-Eun Lee & Anubha Mahajan & Hyun-Young Park & Mark I. McCar, 2022. "The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Ricky Lali & Michael Chong & Arghavan Omidi & Pedrum Mohammadi-Shemirani & Ann Le & Edward Cui & Guillaume Paré, 2021. "Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Saaket Agrawal & Minxian Wang & Marcus D. R. Klarqvist & Kirk Smith & Joseph Shin & Hesam Dashti & Nathaniel Diamant & Seung Hoan Choi & Sean J. Jurgens & Patrick T. Ellinor & Anthony Philippakis & Me, 2022. "Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Stephanie O. Erjavec & Sahar Gelfman & Alexa R. Abdelaziz & Eunice Y. Lee & Isha Monga & Anna Alkelai & Iuliana Ionita-Laza & Lynn Petukhova & Angela M. Christiano, 2022. "Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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