Literature DB >> 29748316

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Honghuang Lin1, Jessica van Setten2, Albert V Smith2, Nathan A Bihlmeyer2, Helen R Warren2, Jennifer A Brody2, Farid Radmanesh2, Leanne Hall2, Niels Grarup2, Martina Müller-Nurasyid2, Thibaud Boutin2, Niek Verweij2, Henry J Lin2, Ruifang Li-Gao2, Marten E van den Berg2, Jonathan Marten2, Stefan Weiss2, Bram P Prins2, Jeffrey Haessler2, Leo-Pekka Lyytikäinen2, Hao Mei2, Tamara B Harris2, Lenore J Launer2, Man Li2, Alvaro Alonso2, Elsayed Z Soliman2, John M Connell2, Paul L Huang2, Lu-Chen Weng2, Heather S Jameson2, William Hucker2, Alan Hanley2, Nathan R Tucker2, Yii-Der Ida Chen2, Joshua C Bis2, Kenneth M Rice2, Colleen M Sitlani2, Jan A Kors2, Zhijun Xie2, Chengping Wen2, Jared W Magnani2, Christopher P Nelson2, Jørgen K Kanters2, Moritz F Sinner2, Konstantin Strauch2, Annette Peters2, Melanie Waldenberger2, Thomas Meitinger2, Jette Bork-Jensen2, Oluf Pedersen2, Allan Linneberg2, Igor Rudan2, Rudolf A de Boer2, Peter van der Meer2, Jie Yao2, Xiuqing Guo2, Kent D Taylor2, Nona Sotoodehnia2, Jerome I Rotter2, Dennis O Mook-Kanamori2, Stella Trompet2, Fernando Rivadeneira2, André Uitterlinden2, Mark Eijgelsheim2, Sandosh Padmanabhan2, Blair H Smith2, Henry Völzke2, Stephan B Felix2, Georg Homuth2, Uwe Völker2, Massimo Mangino2, Timothy D Spector2, Michiel L Bots2, Marco Perez2, Mika Kähönen2, Olli T Raitakari2, Vilmundur Gudnason2, Dan E Arking2, Patricia B Munroe2, Bruce M Psaty2, Cornelia M van Duijn2, Emelia J Benjamin2, Jonathan Rosand2, Nilesh J Samani2, Torben Hansen2, Stefan Kääb2, Ozren Polasek2, Pim van der Harst2, Susan R Heckbert2, J Wouter Jukema2, Bruno H Stricker2, Caroline Hayward2, Marcus Dörr2, Yalda Jamshidi2, Folkert W Asselbergs2, Charles Kooperberg2, Terho Lehtimäki2, James G Wilson2, Patrick T Ellinor2, Steven A Lubitz1, Aaron Isaacs2.   

Abstract

BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.
METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval.
RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus.
CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health.
© 2018 American Heart Association, Inc.

Entities:  

Keywords:  atrioventricular node; genetic loci; genome-wide association study

Mesh:

Year:  2018        PMID: 29748316      PMCID: PMC5951629          DOI: 10.1161/CIRCGEN.117.002037

Source DB:  PubMed          Journal:  Circ Genom Precis Med        ISSN: 2574-8300


  37 in total

1.  Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic.

Authors:  Tao Yang; Thomas C Atack; Dina Myers Stroud; Wei Zhang; Lynn Hall; Dan M Roden
Journal:  Circ Res       Date:  2012-06-20       Impact factor: 17.367

2.  Functional Nav1.8 channels in intracardiac neurons: the link between SCN10A and cardiac electrophysiology.

Authors:  Arie O Verkerk; Carol Ann Remme; Cees A Schumacher; Brendon P Scicluna; Rianne Wolswinkel; Berend de Jonge; Connie R Bezzina; Marieke W Veldkamp
Journal:  Circ Res       Date:  2012-06-20       Impact factor: 17.367

3.  Heritability in a SCN5A-mutation founder population with increased female susceptibility to non-nocturnal ventricular tachyarrhythmia and sudden cardiac death.

Authors:  Rachel M A Ter Bekke; Aaron Isaacs; Andrei Barysenka; Marije B Hoos; Jan D H Jongbloed; Jan C A Hoorntje; Alfons S M Patelski; Apollonia T J M Helderman-van den Enden; Arthur van den Wijngaard; Monika Stoll; Paul G A Volders
Journal:  Heart Rhythm       Date:  2017-08-03       Impact factor: 6.343

4.  Sodium channel mutations and susceptibility to heart failure and atrial fibrillation.

Authors:  Timothy M Olson; Virginia V Michels; Jeffrey D Ballew; Sandra P Reyna; Margaret L Karst; Kathleen J Herron; Steven C Horton; Richard J Rodeheffer; Jeffrey L Anderson
Journal:  JAMA       Date:  2005-01-26       Impact factor: 56.272

5.  Predicting functional effect of human missense mutations using PolyPhen-2.

Authors:  Ivan Adzhubei; Daniel M Jordan; Shamil R Sunyaev
Journal:  Curr Protoc Hum Genet       Date:  2013-01

6.  Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.

Authors:  Anne M Butler; Xiaoyan Yin; Daniel S Evans; Michael A Nalls; Erin N Smith; Toshiko Tanaka; Guo Li; Sarah G Buxbaum; Eric A Whitsel; Alvaro Alonso; Dan E Arking; Emelia J Benjamin; Gerald S Berenson; Josh C Bis; Wei Chen; Rajat Deo; Patrick T Ellinor; Susan R Heckbert; Gerardo Heiss; Wen-Chi Hsueh; Brendan J Keating; Kathleen F Kerr; Yun Li; Marian C Limacher; Yongmei Liu; Steven A Lubitz; Kristin D Marciante; Reena Mehra; Yan A Meng; Anne B Newman; Christopher Newton-Cheh; Kari E North; Cameron D Palmer; Bruce M Psaty; P Miguel Quibrera; Susan Redline; Alex P Reiner; Jerome I Rotter; Renate B Schnabel; Nicholas J Schork; Andrew B Singleton; J Gustav Smith; Elsayed Z Soliman; Sathanur R Srinivasan; Zhu-ming Zhang; Alan B Zonderman; Luigi Ferrucci; Sarah S Murray; Michele K Evans; Nona Sotoodehnia; Jared W Magnani; Christy L Avery
Journal:  Circ Cardiovasc Genet       Date:  2012-11-08

7.  Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects.

Authors:  Maximilian G Posch; Stephan Waldmuller; Melanie Müller; Thomas Scheffold; David Fournier; Miguel A Andrade-Navarro; Bernard De Geeter; Sophie Guillaumont; Claire Dauphin; Dany Yousseff; Katharina R Schmitt; Andreas Perrot; Felix Berger; Roland Hetzer; Patrice Bouvagnet; Cemil Özcelik
Journal:  PLoS One       Date:  2011-12-14       Impact factor: 3.240

8.  Variant Set Enrichment: an R package to identify disease-associated functional genomic regions.

Authors:  Musaddeque Ahmed; Richard C Sallari; Haiyang Guo; Jason H Moore; Housheng Hansen He; Mathieu Lupien
Journal:  BioData Min       Date:  2017-02-22       Impact factor: 2.522

9.  Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.

Authors:  Connie R Bezzina; Julien Barc; Yuka Mizusawa; Carol Ann Remme; Jean-Baptiste Gourraud; Floriane Simonet; Arie O Verkerk; Peter J Schwartz; Lia Crotti; Federica Dagradi; Pascale Guicheney; Véronique Fressart; Antoine Leenhardt; Charles Antzelevitch; Susan Bartkowiak; Martin Borggrefe; Rainer Schimpf; Eric Schulze-Bahr; Sven Zumhagen; Elijah R Behr; Rachel Bastiaenen; Jacob Tfelt-Hansen; Morten Salling Olesen; Stefan Kääb; Britt M Beckmann; Peter Weeke; Hiroshi Watanabe; Naoto Endo; Tohru Minamino; Minoru Horie; Seiko Ohno; Kanae Hasegawa; Naomasa Makita; Akihiko Nogami; Wataru Shimizu; Takeshi Aiba; Philippe Froguel; Beverley Balkau; Olivier Lantieri; Margherita Torchio; Cornelia Wiese; David Weber; Rianne Wolswinkel; Ruben Coronel; Bas J Boukens; Stéphane Bézieau; Eric Charpentier; Stéphanie Chatel; Aurore Despres; Françoise Gros; Florence Kyndt; Simon Lecointe; Pierre Lindenbaum; Vincent Portero; Jade Violleau; Manfred Gessler; Hanno L Tan; Dan M Roden; Vincent M Christoffels; Hervé Le Marec; Arthur A Wilde; Vincent Probst; Jean-Jacques Schott; Christian Dina; Richard Redon
Journal:  Nat Genet       Date:  2013-07-21       Impact factor: 38.330

10.  Mutational analysis of SCN5A gene in long QT syndrome.

Authors:  Sameera Fatima Qureshi; Altaf Ali; Princy John; Amol P Jadhav; Ananthapur Venkateshwari; Hygriv Rao; M P Jayakrishnan; Calambur Narasimhan; Jayaprakash Shenthar; Kumarasamy Thangaraj; Pratibha Nallari
Journal:  Meta Gene       Date:  2015-09-02
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1.  Genome-first approach to rare EYA4 variants and cardio-auditory phenotypes in adults.

Authors:  Shadi Ahmadmehrabi; Binglan Li; Joseph Park; Batsal Devkota; Marijana Vujkovic; Yi-An Ko; David Van Wagoner; W H Wilson Tang; Ian Krantz; Marylyn Ritchie; Jason Brant; Michael J Ruckenstein; Douglas J Epstein; Daniel J Rader
Journal:  Hum Genet       Date:  2021-03-21       Impact factor: 4.132

2.  Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

Authors:  Lu-Chen Weng; Amelia Weber Hall; Seung Hoan Choi; Sean J Jurgens; Jeffrey Haessler; Nathan A Bihlmeyer; Niels Grarup; Honghuang Lin; Alexander Teumer; Ruifang Li-Gao; Jie Yao; Xiuqing Guo; Jennifer A Brody; Martina Müller-Nurasyid; Katharina Schramm; Niek Verweij; Marten E van den Berg; Jessica van Setten; Aaron Isaacs; Julia Ramírez; Helen R Warren; Sandosh Padmanabhan; Jan A Kors; Rudolf A de Boer; Peter van der Meer; Moritz F Sinner; Melanie Waldenberger; Bruce M Psaty; Kent D Taylor; Uwe Völker; Jørgen K Kanters; Man Li; Alvaro Alonso; Marco V Perez; Ilonca Vaartjes; Michiel L Bots; Paul L Huang; Susan R Heckbert; Henry J Lin; Jelena Kornej; Patricia B Munroe; Cornelia M van Duijn; Folkert W Asselbergs; Bruno H Stricker; Pim van der Harst; Stefan Kääb; Annette Peters; Nona Sotoodehnia; Jerome I Rotter; Dennis O Mook-Kanamori; Marcus Dörr; Stephan B Felix; Allan Linneberg; Torben Hansen; Dan E Arking; Charles Kooperberg; Emelia J Benjamin; Kathryn L Lunetta; Patrick T Ellinor; Steven A Lubitz
Journal:  Circ Genom Precis Med       Date:  2020-08-21

3.  Genome-wide association studies of cardiac electrical phenotypes.

Authors:  Charlotte Glinge; Najim Lahrouchi; Reza Jabbari; Jacob Tfelt-Hansen; Connie R Bezzina
Journal:  Cardiovasc Res       Date:  2020-07-15       Impact factor: 10.787

4.  Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.

Authors:  Jessica van Setten; Niek Verweij; Hamdi Mbarek; Maartje N Niemeijer; Stella Trompet; Dan E Arking; Jennifer A Brody; Ilaria Gandin; Niels Grarup; Leanne M Hall; Daiane Hemerich; Leo-Pekka Lyytikäinen; Hao Mei; Martina Müller-Nurasyid; Bram P Prins; Antonietta Robino; Albert V Smith; Helen R Warren; Folkert W Asselbergs; Dorret I Boomsma; Mark J Caulfield; Mark Eijgelsheim; Ian Ford; Torben Hansen; Tamara B Harris; Susan R Heckbert; Jouke-Jan Hottenga; Annamaria Iorio; Jan A Kors; Allan Linneberg; Peter W MacFarlane; Thomas Meitinger; Christopher P Nelson; Olli T Raitakari; Claudia T Silva Aldana; Gianfranco Sinagra; Moritz Sinner; Elsayed Z Soliman; Monika Stoll; Andre Uitterlinden; Cornelia M van Duijn; Melanie Waldenberger; Alvaro Alonso; Paolo Gasparini; Vilmundur Gudnason; Yalda Jamshidi; Stefan Kääb; Jørgen K Kanters; Terho Lehtimäki; Patricia B Munroe; Annette Peters; Nilesh J Samani; Nona Sotoodehnia; Sheila Ulivi; James G Wilson; Eco J C de Geus; J Wouter Jukema; Bruno Stricker; Pim van der Harst; Paul I W de Bakker; Aaron Isaacs
Journal:  Eur J Hum Genet       Date:  2019-01-24       Impact factor: 4.246

5.  GATA6 is a regulator of sinus node development and heart rhythm.

Authors:  Lara Gharibeh; Abir Yamak; Jamieson Whitcomb; Aizhu Lu; Mathieu Joyal; Hiba Komati; Wenbin Liang; Céline Fiset; Mona Nemer
Journal:  Proc Natl Acad Sci U S A       Date:  2020-12-21       Impact factor: 11.205

6.  Model Embraced Electromechanical Coupling Time for Estimation of Heart Failure in Patients With Hypertrophic Cardiomyopathy.

Authors:  Su Hu; Lan Mi; Jianli Fu; Wangxia Ma; Jingsong Ni; Zhenxia Zhang; Botao Li; Gongchang Guan; Junkui Wang; Na Zhao
Journal:  Front Cardiovasc Med       Date:  2022-06-16

Review 7.  Genetics and genomics of arrhythmic risk: current and future strategies to prevent sudden cardiac death.

Authors:  Chiara Scrocco; Connie R Bezzina; Michael J Ackerman; Elijah R Behr
Journal:  Nat Rev Cardiol       Date:  2021-05-24       Impact factor: 32.419

8.  Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Authors:  Seung Hoan Choi; Sean J Jurgens; Christopher M Haggerty; Amelia W Hall; Jennifer L Halford; Valerie N Morrill; Lu-Chen Weng; Braxton Lagerman; Tooraj Mirshahi; Mary Pettinger; Xiuqing Guo; Henry J Lin; Alvaro Alonso; Elsayed Z Soliman; Jelena Kornej; Honghuang Lin; Arden Moscati; Girish N Nadkarni; Jennifer A Brody; Kerri L Wiggins; Brian E Cade; Jiwon Lee; Christina Austin-Tse; Tom Blackwell; Mark D Chaffin; Christina J-Y Lee; Heidi L Rehm; Carolina Roselli; Susan Redline; Braxton D Mitchell; Nona Sotoodehnia; Bruce M Psaty; Susan R Heckbert; Ruth J F Loos; Ramachandran S Vasan; Emelia J Benjamin; Adolfo Correa; Eric Boerwinkle; Dan E Arking; Jerome I Rotter; Stephen S Rich; Eric A Whitsel; Marco Perez; Charles Kooperberg; Brandon K Fornwalt; Kathryn L Lunetta; Patrick T Ellinor; Steven A Lubitz
Journal:  Circ Genom Precis Med       Date:  2021-07-28

9.  MungeSumstats: A Bioconductor package for the standardisation and quality control of many GWAS summary statistics.

Authors:  Alan E Murphy; Brian M Schilder; Nathan G Skene
Journal:  Bioinformatics       Date:  2021-10-02       Impact factor: 6.937

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

Authors:  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; Fabiola Del Greco M; 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 M van Duijn; Paul L Huang; Vilmundur Gudnason; Tamara B Harris; Lenore J Launer; Albert V Smith; Erwin P Bottinger; Ruth J F Loos; Girish N Nadkarni; Michael H Preuss; Adolfo Correa; Hao Mei; James Wilson; Thomas Meitinger; Martina Müller-Nurasyid; Annette Peters; Melanie Waldenberger; Massimo Mangino; Timothy D Spector; Michiel Rienstra; Yordi J 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; Kenneth 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 Völker; 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 H 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 B 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; Daniel F Gudbjartsson; Hilma Holm; Patrick Sulem; Gudmar Thorleifsson; Rosa B Thorolfsdottir; Unnur Thorsteinsdottir; Emelia J Benjamin; Andrew Tinker; Kari Stefansson; Patrick T Ellinor; Yalda Jamshidi; Steven A Lubitz; Patricia B Munroe
Journal:  Nat Commun       Date:  2020-05-21       Impact factor: 17.694

  10 in total

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