Menu Close

Multi-Ancestry GWAS of the Electrocardiographic PR Interval Identifies 202 Loci Underlying Cardiac Conduction

Citation

Ntalla, Ioanna; Weng, Lu-Chen; Cartwright, James H.; Hall, Amelia Webe; Sveinbjornsson, Gardar; Tucker, Nathan R.; Choi, Seung Hoan; Chaffin, Mark D.; Roselli, Carolina; & Barnes, Michael R., et al. (2020). Multi-Ancestry GWAS of the Electrocardiographic PR Interval Identifies 202 Loci Underlying Cardiac Conduction. Nature Communications, 11(1), 2542. PMCID: PMC7242331

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.

URL

http://dx.doi.org/10.1038/s41467-020-15706-x

Reference Type

Journal Article

Journal Title

Nature Communications

Author(s)

Ntalla, Ioanna
Weng, Lu-Chen
Cartwright, James H.
Hall, Amelia Webe
Sveinbjornsson, Gardar
Tucker, Nathan R.
Choi, Seung Hoan
Chaffin, Mark D.
Roselli, Carolina
Barnes, Michael R.
Mifsud, Borbala
Warren, Helen R.
Hayward, Caroline
Marten, Jonathan
Cranley, James J.
Concas, Maria Pina
Gasparini, Paolo
Boutin, Thibaud
Kolcic, Ivana
Polasek, Ozren
Rudan, Igor
Araujo, Nathalia M.
Lima-Costa, Maria Fernanda
Ribeiro, Antonio Luiz P.
Souza, Renan P.
Tarazona-Santos, Eduardo
Giedraitis, Vilmantas
Ingelsson, Erik
Mahajan, Anubha
Morris, Andrew P.
Del Greco M., Fabiola
Foco, Luisa
Gögele, Martin
Hicks, Andrew A.
Cook, James P.
Lind, Lars
Lindgren, Cecilia M.
Sundström, Johan
Nelson, Christopher P.
Riaz, Muhammad B.
Samani, Nilesh J.
Sinagra, Gianfranco
Ulivi, Sheila
Kähönen, Mika
Mishra, Pashupati P.
Mononen, Nina
Nikus, Kjell
Caulfield, Mark J.
Dominiczak, Anna
Padmanabhan, Sandosh
Montasser, May E.
O'Connell, Jeff R.
Ryan, Kathleen
Shuldiner, Alan R.
Aeschbacher, Stefanie
Conen, David
Risch, Lorenz
Thériault, Sébastien
Hutri-Kähönen, Nina
Lehtimäki, Terho
Lyytikäinen, Leo-Pekka
Raitakari, Olli T
Barnes, Catriona L K
Campbell, Harry
Joshi, Peter K.
Wilson, James F.
Isaacs, Aaron
Kors, Jan A.
van Duijn, Cornelia M.
Huang, Paul L.
Gudnason, Vilmundur
Harris, Tamara B.
Launer, Lenore J.
Smith, Albert V.
Bottinger, Erwin P.
Loos, Ruth J. F.
Nadkarni, Girish N.
Preuss, Michael H.
Correa, Adolfo
Mei, Hao
Wilson, James
Meitinger, Thomas
Müller-Nurasyid, Martina
Peters, Annette
Waldenberger, Melanie
Mangino, Massimo
Spector, Timothy D.
Rienstra, Michiel
van de Vegte, Yordi J.
van der Harst, Pim
Verweij, Niek
Kääb, Stefan
Schramm, Katharina
Sinner, Moritz F.
Strauch, Konstantin
Cutler, Michael J.
Fatkin, Diane
London, Barry
Olesen, Morten
Roden, Dan M.
Benjamin Shoemaker, M.
Gustav Smith, J.
Biggs, Mary L.
Bis, Joshua C.
Brody, Jennifer A.
Psaty, Bruce M.
Rice, Kenneth
Sotoodehnia, Nona
De Grandi, Alessandro
Fuchsberger, Christian
Pattaro, Cristian
Pramstaller, Peter P
Ford, Ian
Wouter Jukema, J.
Macfarlane, Peter W.
Trompet, Stella
Dörr, Marcus
Felix, Stephan B.
Völker, Uwe
Weiss, Stefan
Havulinna, Aki S.
Jula, Antti
Sääksjärvi, Katri
Salomaa, Veikko
Guo, Xiuqing
Heckbert, Susan R.
Lin, Henry J.
Rotter, Jerome I.
Taylor, Kent D.
Yao, Jie
de Mutsert, Renée
Maan, Arie C.
Mook-Kanamori, Dennis O.
Noordam, Raymond
Cucca, Francesco
Ding, Jun
Lakatta, Edward G.
Qian, Yong
Tarasov, Kirill V.
Levy, Daniel
Lin, Honghuang
Newton-Cheh, Christopher H.
Lunetta, Kathryn L.
Murray, Alison D.
Porteous, David J.
Smith, Blair H.
Stricker, Bruno H.
Uitterlinden, André
van den Berg, Marten E
Haessler, Jeffrey
Jackson, Rebecca D.
Kooperberg, Charles L.
Peters, Ulrike
Reiner, Alexander P.
Whitsel, Eric A.
Alonso, Alvaro
Arking, Dan E.
Boerwinkle, Eric
Ehret, Georg B.
Soliman, Elsayed Z.
Avery, Christy L.
Gogarten, Stephanie M.
Kerr, Kathleen F.
Laurie, Cathy C.
Seyerle, Amanda A.
Stilp, Adrienne
Assa, Solmaz
Abdullah Said, M.
Yldau van der Ende, M.
Lambiase, Pier D.
Orini, Michele
Ramirez, Julia
Van Duijvenboden, Stefan
Arnar, David O.
Gudbjartsson, Daniel F.
Holm, Hilma
Sulem, Patrick
Thorleifsson, Gudmar
Thorolfsdottir, Rosa B.
Thorsteinsdottir, Unnur
Benjamin, Emelia J.
Tinker, Andrew
Stefansson, Kari
Ellinor, Patrick T.
Jamshidi, Yalda
Lubitz, Steven A.
Munroe, Patricia B.

Year Published

2020

Volume Number

11

Issue Number

1

Pages

2542

PMCID

PMC7242331

Reference ID

12977