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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Title:	PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Authors:	van Setten, Jessica; Brody, Jennifer A.; Jamshidi, Yalda; Swenson, Brenton R.; Butler, Anne M.; Campbell, Harry; Del Greco, Fabiola M.; Evans, Daniel S.; Gibson, Quince; Gudbjartsson, Daniel F.; Kerr, Kathleen F.; Krijthe, Bouwe P.; Lyytikäinen, Leo-Pekka; Müller, Christian; Müller-Nurasyid, Martina; Nolte, Ilja M.; Padmanabhan, Sandosh; Ritchie, Marylyn D.; Robino, Antonietta; Smith, Albert V.; Steri, Maristella; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; Ulivi, Sheila; Verweij, Niek; Yin, Xiaoyan; Arnar, David O.; Asselbergs, Folkert W.; Bader, Joel S.; Barnard, John; Bis, Josh; Blankenberg, Stefan; Boerwinkle, Eric; Bradford, Yuki; Buckley, Brendan M.; Chung, Mina K.; Crawford, Dana; den Hoed, Marcel; Denny, Josh C.; Dominiczak, Anna F.; Ehret, Georg B.; Eijgelsheim, Mark; Ellinor, Patrick T.; Felix, Stephan B.; Franco, Oscar H.; Franke, Lude; Harris, Tamara B.; Holm, Hilma; Ilaria, Gandin; Iorio, Annamaria; Kähönen, Mika; Kolcic, Ivana; Kors, Jan A.; Lakatta, Edward G.; Launer, Lenore J.; Lin, Honghuang; Lin, Henry J.; Loos, Ruth J. F.; Lubitz, Steven A.; Macfarlane, Peter W.; Magnani, Jared W.; Leach, Irene Mateo; Meitinger, Thomas; Mitchell, Braxton D.; Munzel, Thomas; Papanicolaou, George J.; Peters, Annette; Pfeufer, Arne; Pramstaller, Peter P.; Raitakari, Olli T.; Rotter, Jerome I.; Rudan, Igor; Samani, Nilesh J.; Schlessinger, David; Silva Aldana, Claudia T.; Sinner, Moritz F.; Smith, Jonathan D.; Snieder, Harold; Soliman, Elsayed Z.; Spector, Timothy D.; Stott, David J.; Strauch, Konstantin; Tarasov, Kirill V.; Thorsteinsdottir, Unnur; Uitterlinden, Andre G.; Van Wagoner, David R.; Völker, Uwe; Völzke, Henry; Waldenberger, Melanie; Jan Westra, Harm; Wild, Philipp S.; Zeller, Tanja; Alonso, Alvaro; Avery, Christy L.; Bandinelli, Stefania; Benjamin, Emelia J.; Cucca, Francesco; Dörr, Marcus; Ferrucci, Luigi; Gasparini, Paolo; Gudnason, Vilmundur; Hayward, Caroline; Heckbert, Susan R.; Hicks, Andrew A.; Jukema, J. Wouter; Kääb, Stefan; Lehtimäki, Terho; Liu, Yongmei; Munroe, Patricia B.; Parsa, Afshin; Polasek, Ozren; Psaty, Bruce M.; Roden, Dan M.; Schnabel, Renate B.; Sinagra, Gianfranco; Stefansson, Kari; Stricker, Bruno H.; van der Harst, Pim; van Duijn, Cornelia M.; Wilson, James F.; Gharib, Sina A.; de Bakker, Paul I. W.; Isaacs, Aaron; Arking, Dan E.; Sotoodehnia, Nona
Contributors:	Show more 1 Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands Show more 2 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA Show more 3 St Georges Univ London, Cardiogenet Lab, Mol & Clin Sci Res Inst, London SW17 0RE, England Show more 4 Univ Washington, Inst Publ Hlth Genet, Sch Publ Hlth, Seattle, WA 98195 USA Show more 5 Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA Show more 6 Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9YL, Midlothian, Scotland Show more 7 Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, I-39100 Bolzano, Italy Show more 8 Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA Show more 9 Univ Alabama Birmingham Hosp, Dept Surg, Birmingham, AL 35233 USA 10 DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland Show more 11 Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland Show more 12 Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA Show more 13 Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands 14 Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland Show more 15 Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33014, Finland Show more 16 Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany Show more 17 DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany Show more 18 German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany Show more 19 Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, D-81377 Munich, Germany Show more 20 DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany Show more 21 Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713GZ Groningen, Netherlands Show more 22 Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland Show more 23 Univ Penn, Dept Genet, Philadelphia, PA 19104 USA Show more 24 IRCCS Burlo Garofolo, Inst Maternal & Child Health, I-34137 Trieste, Italy 25 Iceland Heart Assoc, IS-201 Kopavogur, Iceland Show more 26 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland Show more 27 Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA Show more 28 CNR, Ist Ric Genet & Biomed, I-00185 Cagliari, Italy Show more 29 NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA Show more 30 Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany Show more 31 DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany Show more 32 Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands Show more 33 Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands Show more 34 Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-7913GZ Groningen, Netherlands Show more 35 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA Show more 36 Landspitali Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland 37 Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands Show more 38 UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England Show more 39 UCL, Farr Inst Hlth Informat Res, London WC1E 6BT, England Show more 40 UCL, Inst Hlth Informat, London WC1E 6BT, England Show more 41 Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA Show more 42 Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA Show more 43 Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA Show more 44 Univ Coll Cork, Dept Pharmacol & Therapeut, Cork T12 K8AF, Ireland Show more 45 Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44195 USA Show more 46 Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA Show more 47 Case Western Reserve Univ, Inst Computat Biol, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA Show more 48 Uppsala Univ, Dept Immunol Genet & Pathol, SE-75105 Uppsala, Sweden Show more 49 Uppsala Univ, Sci Life Lab, SE-75105 Uppsala, Sweden Show more 50 Vanderbilt Univ, Biomed Informat & Med, 221 Kirkland Hall, Nashville, TN 37235 USA Show more 51 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21287 USA Show more 52 Univ Med Ctr Groningen, Dept Nephrol, NL-7913GZ Groningen, Netherlands Show more 53 Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA Show more 54 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA Show more 55 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA Show more 56 Univ Med Greifswald, Dept Internal Med B, D-17489 Greifswald, Germany Show more 57 Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands Show more 58 NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA Show more 59 Univ Trieste, Dept Med Sci, I-34127 Trieste, Italy 60 Osped Riuniti, Cardiovasc Dept, I-34124 Trieste, Italy Show more 61 Univ Trieste, I-34124 Trieste, Italy Show more 62 Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland Show more 63 Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere 33014, Finland Show more 64 Univ Split, Fac Med, Split 21000, Croatia Show more 65 Erasmus Univ, Med Ctr, Dept Med Informat, NL-3015 GD Rotterdam, Netherlands Show more 66 NIA, Lab Cardiovasc Sci, NIH, Bethesda, MD 20892 USA Show more 67 Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA Show more 68 Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA Show more 69 Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA Show more 70 Univ Glasgow, Inst Hlth & Wellbeing, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland Show more 71 Univ Pittsburgh, Med Ctr, Heart & Vasc Inst, Dept Med,Div Cardiol, Pittsburgh, PA 15260 USA Show more 72 German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany Show more 73 Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany Show more 74 Univ Maryland, Geriatr Res & Educ Clin Ctr, Baltimore VA Med Ctr, Dept Med,Sch Med, Baltimore, MD 21201 USA Show more 75 Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, D-55131 Mainz, Germany Show more 76 DZHK German Ctr Cardiovasc Res, Partner Site Rhine Main, D-55131 Mainz, Germany Show more 77 Johannes Gutenberg Univ Mainz, Univ Med Ctr, CTVB, D-55131 Mainz, Germany Show more 78 NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA Show more 79 German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany 80 German Ctr Diabet Res, D-85764 Neuherberg, Germany 81 MVZ Molekulardiagnost, D-81543 Munich, Germany 82 Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy Show more 83 Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland Show more 84 Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland Show more 85 Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90502 USA Show more 86 Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA Show more 87 Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England 88 NIHR Leicester Biomed Res Ctr, Leicester LE3 9QD, Leics, England Show more 89 NIA, Lab Genet & Gen, NIH, Baltimore, MD 20892 USA Show more 90 Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GD Rotterdam, Netherlands Show more 91 Univ Rosario, Sch Med & Hlth Sci, Ctr Res Genet & Genom CIGGUR, GENIUROS Res Grp,Inst Translat Med IMT, Cl 12c 6-25, Bogota, Colombia Show more 92 Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med Biol, Cleveland, OH 44195 USA Show more 93 Wake Forest Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC 27101 USA Show more 94 Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England Show more 95 Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, D-81377 Munich, Germany Show more 96 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland Show more 97 Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands Show more 98 Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17489 Greifswald, Germany Show more 99 German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany Show more 100 Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Prevent Cardiol & Prevent Med, D-55131 Mainz, Germany Show more 101 Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55131 Mainz, Germany Show more 102 Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA Show more 103 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA Show more 104 Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27514 USA 105 ASF, Geriatr Unit, I-50122 Florence, Italy Show more 106 Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH8 9YL, Midlothian, Scotland Show more 107 Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA Show more 108 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA Show more 109 Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands Show more 110 Interuniv Cardiol Inst Netherlands, NL-3511EP Utrecht, Netherlands Show more 111 Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA Show more 112 Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London E1 4NS, England Show more 113 Barts Hlth NHS Trust & Queen Mary Univ London, NIHR Biomed Res Ctr, London E1 4NS, England Show more 114 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA Show more 115 Baltimore VA Med Ctr, Baltimore, MD 21201 USA 116 Psychiat Hosp Sveti Ivan, Zagreb 10000, Croatia 117 Gen Info Ltd, Zagreb 10000, Croatia Show more 118 Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA Show more 119 Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA 120 Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA Show more 121 Vanderbilt Univ, Med Pharmacol & Biomed Informat, Nashville, TN 37235 USA Show more 122 Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands 123 Inspectorate Hlth Care, NL-2511VX The Hague, Netherlands Show more 124 Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands 125 Netherlands Heart Inst, ICIN, Durrer Ctr Cardiogenet Res, NL-3511EP Utrecht, Netherlands Show more 126 Univ Washington, Div Pulm Crit Care & Sleep Med, Computat Med Core Ctr Lung Biol, Cardiovasc Hlth Res Unit,Dept Med, Seattle, WA 98195 USA Show more 127 Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, NL-3584 CX Utrecht, Netherlands Show more 128 Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands 129 CARIM Sch Cardiovasc Dis, NL-6229ER Maastricht, Netherlands Show more 130 Maastricht Univ, Ctr Syst Biol MaCSBio, NL-6229ER Maastricht, Netherlands Show more 131 Maastricht Univ, Dept Biochem, NL-6229ER Maastricht, Netherlands Show more 132 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA Show more 133 Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Med, Seattle, WA 98101 USA Show more 134 Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Epidemiol, Seattle, WA 98101 USA
Publisher Information:	Nature Publishing Group
Publication Year:	2018
Collection:	Hirsla - Landspítali University Hospital research archive
Subject Terms:	Hjartasjúkdómar; Gen; Genamengi; Atrial Fibrillation; Heart Diseases; Heart Block; Genome-Wide Association Study
Description:	To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. ; Bristol Myers Squibb Bayer HealthCare Biotronik Boehringer Ingelheim Bayer AG Amgen AstraZeneca
Document Type:	article in journal/newspaper
Language:	English
ISSN:	2041-1723
Relation:	http://www.nature.com/articles/s41467-018-04766-9; PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity 2018, 9 (1) Nature Communications; http://hdl.handle.net/2336/620667; Nature Communications
DOI:	10.1038/s41467-018-04766-9
Availability:	http://hdl.handle.net/2336/620667; https://doi.org/10.1038/s41467-018-04766-9
Rights:	Archived with thanks to Nature Communications ; Open Access - Opinn aðgangur
Accession Number:	edsbas.ED5CF7C9
Database:	BASE