Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
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...
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| Vydáno v: | Nature communications Ročník 11; číslo 1; s. 2542 - 12 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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London
Nature Publishing Group UK
21.05.2020
Nature Publishing Group Nature Portfolio |
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| ISSN: | 2041-1723, 2041-1723 |
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| 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.
On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci. |
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| AbstractList | 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 atrioventricularpre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci. 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. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci. 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.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. 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. 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. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci. 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. |
| ArticleNumber | 2542 |
| Author | London, Barry Tarazona-Santos, Eduardo Jamshidi, Yalda Psaty, Bruce M. Nikus, Kjell Souza, Renan P. Weiss, Stefan Orini, Michele Gudnason, Vilmundur Jackson, Rebecca D. Caulfield, Mark J. Benjamin Shoemaker, M. Qian, Yong Schramm, Katharina Mifsud, Borbala Kerr, Kathleen F. Loos, Ruth J. F. Wilson, James Brody, Jennifer A. Lindgren, Cecilia M. Rudan, Igor Waldenberger, Melanie Felix, Stephan B. Dörr, Marcus Stefansson, Kari Gasparini, Paolo Thorolfsdottir, Rosa B. Lima-Costa, Maria Fernanda Peters, Annette Cranley, James J. Murray, Alison D. Barnes, Michael R. Del Greco M, Fabiola Aeschbacher, Stefanie Barnes, Catriona L. K. Concas, Maria Pina Hicks, Andrew A. Munroe, Patricia B. Ellinor, Patrick T. Newton-Cheh, Christopher H. Laurie, Cathy C. Hayward, Caroline Ribeiro, Antonio Luiz P. van der Harst, Pim Samani, Nilesh J. Sinagra, Gianfranco Mononen, Nina Boutin, Thibaud Campbell, Harry Shuldiner, Alan R. Kähönen, Mika Mei, Hao Sveinbjornsson, Gardar Taylor, Kent D. Roden, Dan M. Boerwinkle, Eric Nelson, Christopher P. Sotoodehnia, Nona Arnar |
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| CorporateAuthor | Heart Failure and Mechanical Support Institutionen för kliniska vetenskaper, Lund Sektion II Lunds universitet Section II Profile areas and other strong research environments WCMM-Wallenberg Centre for Molecular Medicine Lund University Cardiovascular Epigenetics Molecular Epidemiology and Cardiology WCMM- Wallenberg center för molekylär medicinsk forskning Kardiologi Department of Clinical Sciences, Lund Strategiska forskningsområden (SFO) EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden Faculty of Medicine Strategic research areas (SRA) Medicinska fakulteten Cardiology Profilområden och andra starka forskningsmiljöer |
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| Snippet | The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial... On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and... |
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| SubjectTerms | 45/43 45/61 631/208/205/2138 631/443/592/2727 692/4019/592/75 Abnormalities Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - physiopathology Atria Basic Medicine Cardiac muscle Cardiology and Cardiovascular Disease Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - genetics Cardiovascular Diseases - physiopathology Cardiovascular pathology Clinical Medicine Conduction Cytoskeleton EKG Electrocardiography Endophenotypes Female Fibrillation Gene Expression Gene loci Gene regulation Genes Genetic Loci - genetics Genetic Predisposition to Disease - genetics Genetic relationship Genetic Variation Genome-Wide Association Study Genomes Heritability Humanities and Social Sciences Humans Implantation Kardiologi och kardiovaskulära sjukdomar Klinisk medicin Male Medical and Health Sciences Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Morbidity Mortality multidisciplinary Multifactorial Inheritance Muscle contraction Muscles Quantitative Trait Loci - genetics Science Science (multidisciplinary) Surgical implants |
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| Title | Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction |
| URI | https://link.springer.com/article/10.1038/s41467-020-15706-x https://www.ncbi.nlm.nih.gov/pubmed/32439900 https://www.proquest.com/docview/2405596020 https://www.proquest.com/docview/2406304403 https://pubmed.ncbi.nlm.nih.gov/PMC7242331 https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-414656 https://doaj.org/article/f435c44c244442da8097cb2f6793771f |
| Volume | 11 |
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