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Nat Commun DOI:10.1038/s41467-020-15706-x

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Publication TypeJournal Article
Year of Publication2020
AuthorsNtalla, I, Weng, L-C, Cartwright, JH, Hall, AWeber, Sveinbjornsson, G, Tucker, NR, Choi, SHoan, Chaffin, MD, Roselli, C, Barnes, MR, Mifsud, B, Warren, HR, Hayward, C, Marten, J, Cranley, JJ, Concas, MPina, Gasparini, P, Boutin, T, Kolcic, I, Polasek, O, Rudan, I, Araujo, NM, Lima-Costa, MFernanda, Ribeiro, ALuiz P, Souza, RP, Tarazona-Santos, E, Giedraitis, V, Ingelsson, E, Mahajan, A, Morris, AP, M, FDel Greco, Foco, L, Gögele, M, Hicks, AA, Cook, JP, Lind, L, Lindgren, CM, Sundstrom, J, Nelson, CP, Riaz, MB, Samani, NJ, Sinagra, G, Ulivi, S, Kähönen, M, Mishra, PP, Mononen, N, Nikus, K, Caulfield, MJ, Dominiczak, A, Padmanabhan, S, Montasser, ME, O'Connell, JR, Ryan, K, Shuldiner, AR, Aeschbacher, S, Conen, D, Risch, L, Thériault, S, Hutri-Kähönen, N, Lehtimäki, T, Lyytikäinen, L-P, Raitakari, OT, Barnes, CLK, Campbell, H, Joshi, PK, Wilson, JF, Isaacs, A, Kors, JA, van Duijn, CM, Huang, PL, Gudnason, V, Harris, TB, Launer, LJ, Smith, AV, Bottinger, EP, Loos, RJF, Nadkarni, GN, Preuss, MH, Correa, A, Mei, H, Wilson, J, Meitinger, T, Müller-Nurasyid, M, Peters, A, Waldenberger, M, Mangino, M, Spector, TD, Rienstra, M, van de Vegte, YJ, van der Harst, P, Verweij, N, Kääb, S, Schramm, K, Sinner, MF, Strauch, K, Cutler, MJ, Fatkin, D, London, B, Olesen, M, Roden, DM, M Shoemaker, B, Gustav Smith, J, Biggs, ML, Bis, JC, Brody, JA, Psaty, BM, Rice, K, Sotoodehnia, N, De Grandi, A, Fuchsberger, C, Pattaro, C, Pramstaller, PP, Ford, I, J Jukema, W, Macfarlane, PW, Trompet, S, Dorr, M, Felix, SB, Volker, U, Weiss, S, Havulinna, AS, Jula, A, Sääksjärvi, K, Salomaa, V, Guo, X, Heckbert, SR, Lin, HJ, Rotter, JI, Taylor, KD, Yao, J, de Mutsert, R, Maan, AC, Mook-Kanamori, DO, Noordam, R, Cucca, F, Ding, J, Lakatta, EG, Qian, Y, Tarasov, KV, Levy, D, Lin, H, Newton-Cheh, CH, Lunetta, KL, Murray, AD, Porteous, DJ, Smith, BH, Stricker, BH, Uitterlinden, A, Van Den Berg, ME, Haessler, J, Jackson, RD, Kooperberg, C, Peters, U, Reiner, AP, Whitsel, EA, Alonso, A, Arking, DE, Boerwinkle, E, Ehret, GB, Soliman, EZ, Avery, CL, Gogarten, SM, Kerr, KF, Laurie, CC, Seyerle, AA, Stilp, A, Assa, S, M Said, A, M van der Ende, Y, Lambiase, PD, Orini, M, Ramirez, J, Van Duijvenboden, S, Arnar, DO, Gudbjartsson, DF, Holm, H, Sulem, P, Thorleifsson, G, Thorolfsdottir, RB, Thorsteinsdottir, U, Benjamin, EJ, Tinker, A, Stefansson, K, Ellinor, PT, Jamshidi, Y, Lubitz, SA, Munroe, PB
JournalNat Commun
Volume11
Issue1
Pages2542
Date Published2020 May 21
ISSN2041-1723
Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

DOI10.1038/s41467-020-15706-x
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/32439900?dopt=Abstract

Alternate JournalNat Commun
PubMed ID32439900