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Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.
van Setten, Jessica; Verweij, Niek; Mbarek, Hamdi; Niemeijer, Maartje N; Trompet, Stella; Arking, Dan E; Brody, Jennifer A; Gandin, Ilaria; Grarup, Niels; Hall, Leanne M; Hemerich, Daiane; Lyytikäinen, Leo-Pekka; Mei, Hao; Müller-Nurasyid, Martina; Prins, Bram P; Robino, Antonietta; Smith, Albert V; Warren, Helen R; Asselbergs, Folkert W; Boomsma, Dorret I; Caulfield, Mark J; Eijgelsheim, Mark; Ford, Ian; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Hottenga, Jouke-Jan; Iorio, Annamaria; Kors, Jan A; Linneberg, Allan; MacFarlane, Peter W; Meitinger, Thomas; Nelson, Christopher P; Raitakari, Olli T; Silva Aldana, Claudia T; Sinagra, Gianfranco; Sinner, Moritz; Soliman, Elsayed Z; Stoll, Monika; Uitterlinden, Andre; van Duijn, Cornelia M; Waldenberger, Melanie; Alonso, Alvaro; Gasparini, Paolo; Gudnason, Vilmundur; Jamshidi, Yalda; Kääb, Stefan; Kanters, Jørgen K; Lehtimäki, Terho; Munroe, Patricia B.
Affiliation
  • van Setten J; Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands. J.vanSetten@umcutrecht.nl.
  • Verweij N; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Mbarek H; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Niemeijer MN; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Trompet S; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Arking DE; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Brody JA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gandin I; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Grarup N; Research Unit, AREA Science Park, Trieste, Italy.
  • Hall LM; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Hemerich D; Department of Cardiovascular Sciences, University of Leicester, Leicester, England.
  • Lyytikäinen LP; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby Road, Leicester, UK.
  • Mei H; Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
  • Müller-Nurasyid M; CAPES Foundation, Ministry of Education of Brazil, Brasília, DF, 70040-020, Brazil.
  • Prins BP; Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, 33520, Tampere, Finland.
  • Robino A; Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Smith AV; Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Warren HR; Department of Medicine I, Ludwig-Maximilians-Universität, Munich, Germany.
  • Asselbergs FW; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Boomsma DI; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany.
  • Caulfield MJ; Human Genetics Research Centre, ICCS, St George's University of London, London, UK.
  • Eijgelsheim M; Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
  • Ford I; Icelandic Heart Association, Kopavogur, Iceland.
  • Hansen T; Faculty of Medicine, University of Iceland, Reykavik, Iceland.
  • Harris TB; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
  • Heckbert SR; NIHR Barts Cardiovascular Research Centre, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
  • Hottenga JJ; Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
  • Iorio A; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands.
  • Kors JA; Institute of Cardiovascular Science, Faculty of Population Health Sciences, and Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, London, UK.
  • Linneberg A; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • MacFarlane PW; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
  • Meitinger T; NIHR Barts Cardiovascular Research Centre, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
  • Nelson CP; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Raitakari OT; Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
  • Silva Aldana CT; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
  • Sinagra G; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Sinner M; Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA.
  • Soliman EZ; Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Stoll M; Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Uitterlinden A; Cardiovascular Department, "Ospedali Riuniti and University of Trieste", Trieste, Italy.
  • van Duijn CM; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Waldenberger M; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital-The Capital Region, Copenhagen, Denmark.
  • Alonso A; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Gasparini P; Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
  • Gudnason V; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Jamshidi Y; Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Kääb S; Institute of Human Genetics, Technische Universität München, Munich, Germany.
  • Kanters JK; Department of Cardiovascular Sciences, University of Leicester, Leicester, England.
  • Lehtimäki T; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby Road, Leicester, UK.
  • Munroe PB; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
Eur J Hum Genet ; 27(6): 952-962, 2019 06.
Article de En | MEDLINE | ID: mdl-30679814
ABSTRACT
Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Polymorphisme de nucléotide simple / Électrocardiographie / Locus génétiques Type d'étude: Clinical_trials / Risk_factors_studies / Systematic_reviews Limites: Female / Humans / Male Pays/Région comme sujet: Europa Langue: En Journal: Eur J Hum Genet Sujet du journal: GENETICA MEDICA Année: 2019 Type de document: Article Pays d'affiliation: Pays-Bas
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Polymorphisme de nucléotide simple / Électrocardiographie / Locus génétiques Type d'étude: Clinical_trials / Risk_factors_studies / Systematic_reviews Limites: Female / Humans / Male Pays/Région comme sujet: Europa Langue: En Journal: Eur J Hum Genet Sujet du journal: GENETICA MEDICA Année: 2019 Type de document: Article Pays d'affiliation: Pays-Bas