A1 Refereed original research article in a scientific journal
PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Authors: van Setten J, Brody JA, Jamshidi Y, Swenson BR, Butler AM, Campbell H, Del Greco FM, Evans DS, Gibson Q, Gudbjartsson DF, Kerr KF, Krijthe BP, Lyytikainen LP, Muller C, Muller-Nurasyid M, Nolte IM, Padmanabhan S, Ritchie MD, Robino A, Smith AV, Steri M, Tanaka T, Teumer A, Trompet S, Ulivi S, Verweij N, Yin XY, Arnar DO, Asselbergs FW, Bader JS, Barnard J, Bis J, Blankenberg S, Boerwinkle E, Bradford Y, Buckley BM, Chung MK, Crawford D, den Hoed M, Denny JC, Dominiczak AF, Ehret GB, Eijgelsheim M, Ellinor PT, Felix SB, Franco OH, Franke L, Harris TB, Holm H, Ilaria G, Iorio A, Kahonen M, Kolcic I, Kors JA, Lakatta EG, Launer LJ, Lin HH, Lin HJ, Loos RJF, Lubitz SA, Macfarlane PW, Magnani JW, Leach IM, Meitinger T, Mitchell BD, Munzel T, Papanicolaou GJ, Peters A, Pfeufer A, Pramstaller PP, Raitakari OT, Rotter JI, Rudan I, Samani NJ, Schlessinger D, Aldana CTS, Sinner MF, Smith JD, Snieder H, Soliman EZ, Spector TD, Stott DJ, Strauch K, Tarasov KV, Thorsteinsdottir U, Uitterlinden AG, Van Wagoner DR, Volker U, Volzke H, Waldenberger M, Westra HJ, Wild PS, Zeller T, Alonso A, Avery CL, Bandinelli S, Benjamin EJ, Cucca F, Dorr M, Ferrucci L, Gasparini P, Gudnason V, Hayward C, Heckbert SR, Hicks AA, Jukema JW, Kaab S, Lehtimaki T, Liu YM, Munroe PB, Parsa A, Polasek O, Psaty BM, Roden DM, Schnabel RB, Sinagra G, Stefansson K, Stricker BH, van der Harst P, van Duijn CM, Wilson JF, Gharib SA, de Bakker PIW, Isaacs A, Arking DE, Sotoodehnia N, Sotoodehnia N, Arking DE, Isaacs A, de Bakker PIW, Gharib SA, Wilson JF
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: 2904
Volume: 9
Number of pages: 11
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-04766-9
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/35442531
Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide 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 overrepresented 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 similar to 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, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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