Multi-ancestry GWAS of the electrocardiographic PR interval identifies 210 loci underlying cardiac conduction
By
Ioanna Ntalla,
Lu-Chen Weng,
James H. Cartwright,
Amelia Weber Hall,
Gardar Sveinbjornsson,
Nathan R Tucker,
Seung Hoan Choi,
Mark D. Chaffin,
Carolina Roselli,
Michael R. Barnes,
Borbala Mifsud,
Helen R. Warren,
Caroline Hayward,
Jonathan Marten,
James J. Cranley,
Maria Pina Concas,
Paolo Gasparini,
Thibaud Boutin,
Ivana Kolcic,
Ozren Polasek,
Igor Rudan,
Nathalia M Araujo,
Maria Fernanda Lima-Costa,
Antonio Luiz P. Ribeiro,
Renan P. Souza,
Eduardo Tarazona-Santos,
Vilmantas Giedraitis,
Erik Ingelsson,
Anubha Mahajan,
Andrew P Morris,
Greco M Fabiola Del,
Luisa Foco,
Martin Gögele,
Andrew A. Hicks,
James P Cook,
Lars Lind,
Cecilia M Lindgren,
Johan Sundström,
Christopher P Nelson,
Muhammad B. Riaz,
Nilesh J. Samani,
Gianfranco Sinagra,
Sheila Ulivi,
Mika Kähönen,
Pashupati P. Mishra,
Nina Mononen,
Kjell Nikus,
Mark J. Caulfield,
Anna Dominiczak,
Sandosh Padmanabhan,
May E Montasser,
Jeff R. O’Connell,
Kathleen Ryan,
Alan R. Shuldiner,
Stefanie Aeschbacher,
David Conen,
Lorenz Risch,
Sébastien Thériault,
Nina Hutri-Kähönen,
Terho Lehtimäki,
Leo-Pekka Lyytikäinen,
Olli T. Raitakari,
Catriona L. K. Barnes,
Harry Campbell,
Peter K Joshi,
James F Wilson,
Aaron Isaacs,
Jan A. Kors,
Cornelia Van Duijn,
Paul L. Huang,
Vilmundur Gudnason,
Tamara B. Harris,
Lenore J Launer,
Albert V Smith,
Erwin P. Bottinger,
Ruth J.F. Loos,
Girish Nadkarni,
Michael H Preuss,
Adolfo Correa,
Hao Mei,
James Wilson,
Thomas Meitinger,
Martina Müller-Nuraysid,
Annette Peters,
Melanie Waldenberger,
Massimo Mangino,
Timothy D. Spector,
Michiel Rienstra,
Yordi van de Vegte,
Pim van der Harst,
Niek Verweij,
Stefan Kääb,
Katharina Schramm,
Moritz F. Sinner,
Konstantin Strauch,
Michael J. Cutler,
Diane Fatkin,
Barry London,
Morten Olesen,
Dan M. Roden,
M. Benjamin Shoemaker,
J. Gustav Smith,
Mary L Biggs,
Joshua C Bis,
Jennifer A Brody,
Bruce M Psaty,
Ken Rice,
Nona Sotoodehnia,
Alessandro De Grandi,
Christian Fuchsberger,
Cristian Pattaro,
Peter P. Pramstaller,
Ian Ford,
J. Wouter Jukema,
Peter W. Macfarlane,
Stella Trompet,
Marcus Dörr,
Stephan B. Felix,
Uwe Volker,
Stefan Weiß,
Aki S. Havulinna,
Antti Jula,
Katri Sääksjärvi,
Veikko Salomaa,
Xiuqing Guo,
Susan R. Heckbert,
Henry J Lin,
Jerome I. Rotter,
Kent D Taylor,
Jie Yao,
Renée de Mutsert,
Arie C. Maan,
Dennis O. Mook-Kanamori,
Raymond Noordam,
Francesco Cucca,
Jun Ding,
Edward G Lakatta,
Yong Qian,
Kirill V. Tarasov,
Daniel Levy,
Honghuang Lin,
Christopher Newton-Cheh,
Kathryn L. Lunetta,
Alison D Murray,
David J Porteous,
Blair H Smith,
Bruno H. Stricker,
André Uitterlinden,
Marten E. van den Berg,
Jeffrey Haessler,
Rebecca D Jackson,
Charles Kooperberg,
Ulrike Peters,
Alexander P. Reiner,
Eric A Whitsel,
Alvaro Alonso,
Dan E Arking,
Eric Boerwinkle,
Georg Ehret,
Elsayed Z. Soliman,
Christy L. Avery,
Stephanie M Gogarten,
Kathleen F Kerr,
Cathy C Laurie,
Amanda A. Seyerle,
Adrienne Stilp,
Solmaz Assa,
M. Abdullah Said,
M. Yldau van der Ende,
Pier D. Lambiase,
Michele Orini,
Julia Ramirez,
Stefan Van Duijvenboden,
David O. Arnar,
D.F. Gudbjartsson,
Hilma Holm,
Patrick Sulem,
Gudmar Thorleifsson,
Rosa B. Thorolfsdottir,
Unnur Thorsteinsdottir,
Emelia J. Benjamin,
Andrew Tinker,
Kári Stefánsson,
Patrick T. Ellinor,
Yalda Jamshidi,
Steven A. Lubitz,
Patricia B Munroe
Posted 24 Jul 2019
bioRxiv DOI: 10.1101/712398
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality[1][1],[2][2]. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. [1]: #ref-1 [2]: #ref-2
Download data
- Downloaded 568 times
- Download rankings, all-time:
- Site-wide: 37,022 out of 118,083
- In genetics: 1,867 out of 5,130
- Year to date:
- Site-wide: 38,262 out of 118,083
- Since beginning of last month:
- Site-wide: 55,543 out of 118,083
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!