Nature Communications (Sep 2022)
Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- William J. Young,
- Najim Lahrouchi,
- Aaron Isaacs,
- ThuyVy Duong,
- Luisa Foco,
- Farah Ahmed,
- Jennifer A. Brody,
- Reem Salman,
- Raymond Noordam,
- Jan-Walter Benjamins,
- Jeffrey Haessler,
- Leo-Pekka Lyytikäinen,
- Linda Repetto,
- Maria Pina Concas,
- Marten E. van den Berg,
- Stefan Weiss,
- Antoine R. Baldassari,
- Traci M. Bartz,
- James P. Cook,
- Daniel S. Evans,
- Rebecca Freudling,
- Oliver Hines,
- Jonas L. Isaksen,
- Honghuang Lin,
- Hao Mei,
- Arden Moscati,
- Martina Müller-Nurasyid,
- Casia Nursyifa,
- Yong Qian,
- Anne Richmond,
- Carolina Roselli,
- Kathleen A. Ryan,
- Eduardo Tarazona-Santos,
- Sébastien Thériault,
- Stefan van Duijvenboden,
- Helen R. Warren,
- Jie Yao,
- Dania Raza,
- Stefanie Aeschbacher,
- Gustav Ahlberg,
- Alvaro Alonso,
- Laura Andreasen,
- Joshua C. Bis,
- Eric Boerwinkle,
- Archie Campbell,
- Eulalia Catamo,
- Massimiliano Cocca,
- Michael J. Cutler,
- Dawood Darbar,
- Alessandro De Grandi,
- Antonio De Luca,
- Jun Ding,
- Christina Ellervik,
- Patrick T. Ellinor,
- Stephan B. Felix,
- Philippe Froguel,
- Christian Fuchsberger,
- Martin Gögele,
- Claus Graff,
- Mariaelisa Graff,
- Xiuqing Guo,
- Torben Hansen,
- Susan R. Heckbert,
- Paul L. Huang,
- Heikki V. Huikuri,
- Nina Hutri-Kähönen,
- M. Arfan Ikram,
- Rebecca D. Jackson,
- Juhani Junttila,
- Maryam Kavousi,
- Jan A. Kors,
- Thiago P. Leal,
- Rozenn N. Lemaitre,
- Henry J. Lin,
- Lars Lind,
- Allan Linneberg,
- Simin Liu,
- Peter W. MacFarlane,
- Massimo Mangino,
- Thomas Meitinger,
- Massimo Mezzavilla,
- Pashupati P. Mishra,
- Rebecca N. Mitchell,
- Nina Mononen,
- May E. Montasser,
- Alanna C. Morrison,
- Matthias Nauck,
- Victor Nauffal,
- Pau Navarro,
- Kjell Nikus,
- Guillaume Pare,
- Kristen K. Patton,
- Giulia Pelliccione,
- Alan Pittman,
- David J. Porteous,
- Peter P. Pramstaller,
- Michael H. Preuss,
- Olli T. Raitakari,
- Alexander P. Reiner,
- Antonio Luiz P. Ribeiro,
- Kenneth M. Rice,
- Lorenz Risch,
- David Schlessinger,
- Ulrich Schotten,
- Claudia Schurmann,
- Xia Shen,
- M. Benjamin Shoemaker,
- Gianfranco Sinagra,
- Moritz F. Sinner,
- Elsayed Z. Soliman,
- Monika Stoll,
- Konstantin Strauch,
- Kirill Tarasov,
- Kent D. Taylor,
- Andrew Tinker,
- Stella Trompet,
- André Uitterlinden,
- Uwe Völker,
- Henry Völzke,
- Melanie Waldenberger,
- Lu-Chen Weng,
- Eric A. Whitsel,
- James G. Wilson,
- Christy L. Avery,
- David Conen,
- Adolfo Correa,
- Francesco Cucca,
- Marcus Dörr,
- Sina A. Gharib,
- Giorgia Girotto,
- Niels Grarup,
- Caroline Hayward,
- Yalda Jamshidi,
- Marjo-Riitta Järvelin,
- J. Wouter Jukema,
- Stefan Kääb,
- Mika Kähönen,
- Jørgen K. Kanters,
- Charles Kooperberg,
- Terho Lehtimäki,
- Maria Fernanda Lima-Costa,
- Yongmei Liu,
- Ruth J. F. Loos,
- Steven A. Lubitz,
- Dennis O. Mook-Kanamori,
- Andrew P. Morris,
- Jeffrey R. O’Connell,
- Morten Salling Olesen,
- Michele Orini,
- Sandosh Padmanabhan,
- Cristian Pattaro,
- Annette Peters,
- Bruce M. Psaty,
- Jerome I. Rotter,
- Bruno Stricker,
- Pim van der Harst,
- Cornelia M. van Duijn,
- Niek Verweij,
- James F. Wilson,
- Dan E. Arking,
- Julia Ramirez,
- Pier D. Lambiase,
- Nona Sotoodehnia,
- Borbala Mifsud,
- Christopher Newton-Cheh,
- Patricia B. Munroe
Affiliations
- William J. Young
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Najim Lahrouchi
- Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences
- Aaron Isaacs
- Deptartment of Physiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University
- ThuyVy Duong
- McKusick‐Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine
- Luisa Foco
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Farah Ahmed
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Jennifer A. Brody
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Reem Salman
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Raymond Noordam
- Department of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical Center
- Jan-Walter Benjamins
- University of Groningen, University Medical Center Groningen, Department of Cardiology
- Jeffrey Haessler
- Public Health Sciences Division, Fred Hutchinson Cancer Center
- Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories
- Linda Repetto
- Centre for Global Health Research, Usher Institute, University of Edinburgh
- Maria Pina Concas
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Marten E. van den Berg
- Department of Epidemiology, Erasmus MC – University Medical Center
- Stefan Weiss
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Antoine R. Baldassari
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Traci M. Bartz
- Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington
- James P. Cook
- Department of Health Data Science, University of Liverpool
- Daniel S. Evans
- California Pacific Medical Center, Research Institute
- Rebecca Freudling
- Department of Cardiology, University Hospital, LMU Munich
- Oliver Hines
- Genetics Research Centre, St George’s University of London
- Jonas L. Isaksen
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen
- Honghuang Lin
- National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
- Hao Mei
- Department of Data Science, University of Mississippi Medical Center
- Arden Moscati
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Martina Müller-Nurasyid
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Casia Nursyifa
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Yong Qian
- Translational Gerontology Branch, National Institute on Aging, National Institute of Health
- Anne Richmond
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital
- Carolina Roselli
- University of Groningen, University Medical Center Groningen, Department of Cardiology
- Kathleen A. Ryan
- Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine
- Eduardo Tarazona-Santos
- Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais
- Sébastien Thériault
- Population Health Research Institute, McMaster University
- Stefan van Duijvenboden
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Helen R. Warren
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Jie Yao
- Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
- Dania Raza
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Stefanie Aeschbacher
- Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel
- Gustav Ahlberg
- Laboratory for Molecular Cardiology, The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
- Alvaro Alonso
- Department of Epidemiology, Rollins School of Public Health, Emory University
- Laura Andreasen
- Laboratory for Molecular Cardiology, The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
- Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Eric Boerwinkle
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Archie Campbell
- Usher Institute, University of Edinburgh, Nine, Edinburgh Bioquarter
- Eulalia Catamo
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Massimiliano Cocca
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Michael J. Cutler
- Intermountain Heart Institute, Intermountain Medical Center
- Dawood Darbar
- Department of Medicine, University of Illinois at Chicago
- Alessandro De Grandi
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Antonio De Luca
- Cardiothoracovascular Department, ASUGI, University of Trieste
- Jun Ding
- Translational Gerontology Branch, National Institute on Aging, National Institute of Health
- Christina Ellervik
- Department of Data and Data Support, Region Zealand
- Patrick T. Ellinor
- Cardiovascular Disease Initiative, Broad Institute
- Stephan B. Felix
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Philippe Froguel
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London
- Christian Fuchsberger
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Martin Gögele
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Claus Graff
- Department of Health Science and Technology, Aalborg University
- Mariaelisa Graff
- Department of Epidemiology, University of North Carolina at Chapel Hill
- Xiuqing Guo
- Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
- Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Susan R. Heckbert
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Paul L. Huang
- Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital
- Heikki V. Huikuri
- Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu
- Nina Hutri-Kähönen
- Department of Pediatrics, Tampere University Hospital
- M. Arfan Ikram
- Department of Epidemiology, Erasmus MC – University Medical Center
- Rebecca D. Jackson
- Center for Clinical and Translational Science, Ohio State Medical Center
- Juhani Junttila
- Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu
- Maryam Kavousi
- Department of Epidemiology, Erasmus MC – University Medical Center
- Jan A. Kors
- Department of Medical Informatics, Erasmus University Medical Center
- Thiago P. Leal
- Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais
- Rozenn N. Lemaitre
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Henry J. Lin
- Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
- Lars Lind
- Deptartment of Medical Sciences, Uppsala University
- Allan Linneberg
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital
- Simin Liu
- Center for Global Cardiometabolic Health, Departments of Epidemiology, Medicine and Surgery, Brown University
- Peter W. MacFarlane
- Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow
- Massimo Mangino
- Department of Twin Research and Genetic Epidemiology, King’s College London
- Thomas Meitinger
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Massimo Mezzavilla
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Pashupati P. Mishra
- Department of Clinical Chemistry, Fimlab Laboratories
- Rebecca N. Mitchell
- McKusick‐Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine
- Nina Mononen
- Department of Clinical Chemistry, Fimlab Laboratories
- May E. Montasser
- Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine
- Alanna C. Morrison
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Matthias Nauck
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Victor Nauffal
- Cardiovascular Disease Initiative, Broad Institute
- Pau Navarro
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
- Kjell Nikus
- Department of Cardiology, Heart Center, Tampere University Hospital
- Guillaume Pare
- Population Health Research Institute, McMaster University
- Kristen K. Patton
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Giulia Pelliccione
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Alan Pittman
- Genetics Research Centre, St George’s University of London
- David J. Porteous
- Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital
- Peter P. Pramstaller
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Michael H. Preuss
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Olli T. Raitakari
- Centre for Population Health Research, University of Turku and Turku University Hospital
- Alexander P. Reiner
- Department of Epidemiology/University of Washington
- Antonio Luiz P. Ribeiro
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil
- Kenneth M. Rice
- Department of Biostatistics, University of Washington
- Lorenz Risch
- Labormedizinisches zentrum Dr. Risch
- David Schlessinger
- Laboratory of Genetics and Genomics, National Institute on Aging, National Institute of Health
- Ulrich Schotten
- Deptartment of Physiology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University
- Claudia Schurmann
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Xia Shen
- Centre for Global Health Research, Usher Institute, University of Edinburgh
- M. Benjamin Shoemaker
- Department of Medicine, Division of Cardiovascular Medicine, Arrhythmia Section, Vanderbilt University Medical Center
- Gianfranco Sinagra
- Cardiothoracovascular Department, ASUGI, University of Trieste
- Moritz F. Sinner
- Department of Cardiology, University Hospital, LMU Munich
- Elsayed Z. Soliman
- Epidemiological Cardiology Research Center EPICARE, Wake Forest School of Medicine
- Monika Stoll
- Maastricht Center for Systems Biology MaCSBio, Maastricht University
- Konstantin Strauch
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Kirill Tarasov
- Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institute of Health
- Kent D. Taylor
- Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
- Andrew Tinker
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Stella Trompet
- Department of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical Center
- André Uitterlinden
- Internal Medicine, Erasmus MC
- Uwe Völker
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Henry Völzke
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Melanie Waldenberger
- DZHK (German Centre for Cardiovascular Research, partner site: Munich Heart Alliance
- Lu-Chen Weng
- Cardiovascular Disease Initiative, Broad Institute
- Eric A. Whitsel
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- James G. Wilson
- Department of Physiology and Biophysics, University of Mississippi Medical Center
- Christy L. Avery
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- David Conen
- Population Health Research Institute, McMaster University
- Adolfo Correa
- Departments of Medicine, Pediatrics and Population Health Science, University of Mississippi Medical Center
- Francesco Cucca
- Institute of Genetic and Biomedical Rsearch, Italian National Research Council
- Marcus Dörr
- DZHK German Centre for Cardiovascular Research; partner site Greifswald
- Sina A. Gharib
- Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington
- Giorgia Girotto
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
- Niels Grarup
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Caroline Hayward
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital
- Yalda Jamshidi
- Genetics Research Centre, St George’s University of London
- Marjo-Riitta Järvelin
- Center for Life Course Health Research, Faculty of Medicine, University of Oulu
- J. Wouter Jukema
- Department of Cardiology, Leiden University Medical Center
- Stefan Kääb
- Department of Cardiology, University Hospital, LMU Munich
- Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital
- Jørgen K. Kanters
- Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen
- Charles Kooperberg
- Public Health Sciences Division, Fred Hutchinson Cancer Center
- Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories
- Maria Fernanda Lima-Costa
- Instituto René Rachou, fundação Oswaldo Cruz
- Yongmei Liu
- Department of Medicine, Duke University
- Ruth J. F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Steven A. Lubitz
- Cardiovascular Disease Initiative, Broad Institute
- Dennis O. Mook-Kanamori
- Department of Clinical Epidemiology, Leiden University Medical Center
- Andrew P. Morris
- Department of Health Data Science, University of Liverpool
- Jeffrey R. O’Connell
- Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine
- Morten Salling Olesen
- Department of Biomedical Sciences, University of Copenhagen
- Michele Orini
- Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trust
- Sandosh Padmanabhan
- Institute of Cardiovascular and Medical Sciences, University of Glasgow
- Cristian Pattaro
- Eurac Research, Institute for Biomedicine affiliated with the University of Lübeck
- Annette Peters
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Bruce M. Psaty
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Jerome I. Rotter
- Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
- Bruno Stricker
- Department of Epidemiology, Erasmus MC – University Medical Center
- Pim van der Harst
- University of Groningen, University Medical Center Groningen, Department of Cardiology
- Cornelia M. van Duijn
- Nuffield Department of Population Health, University of Oxford
- Niek Verweij
- University of Groningen, University Medical Center Groningen, Department of Cardiology
- James F. Wilson
- Centre for Global Health Research, Usher Institute, University of Edinburgh
- Dan E. Arking
- McKusick‐Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine
- Julia Ramirez
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Pier D. Lambiase
- Barts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trust
- Nona Sotoodehnia
- Cardiovascular Health Research Unit, Division of Cardiology, Department of Medicine, University of Washington
- Borbala Mifsud
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- Christopher Newton-Cheh
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- Patricia B. Munroe
- William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London
- DOI
- https://doi.org/10.1038/s41467-022-32821-z
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.
