1. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation
- Author
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Michiel L. Bots, Annette Peters, Jennifer A. Brody, Pim van der Harst, Niek Verweij, Torben Hansen, Lu-Chen Weng, Marco V Perez, Honghuang Lin, Nona Sotoodehnia, Katharina Schramm, Dennis O. Mook-Kanamori, Marcus Dörr, Susan R. Heckbert, Henry J. Lin, Jie Yao, Paul L. Huang, Melanie Waldenberger, Bruno H. Stricker, Cornelia M. van Duijn, Jelena Kornej, Kent D. Taylor, Stephan B. Felix, Julia Ramirez, Xiuqing Guo, Peter van der Meer, Patrick T. Ellinor, Emelia J. Benjamin, Amelia W. Hall, Martina Müller-Nurasyid, Steven A. Lubitz, Alexander Teumer, Ilonca Vaartjes, Niels Grarup, Kathryn L. Lunetta, Marten E. van den Berg, Aaron Isaacs, Uwe Völker, Bruce M. Psaty, Jan A. Kors, Alvaro Alonso, Seung Hoan Choi, Rudolf A. de Boer, Allan Linneberg, Sandosh Padmanabhan, Helen R. Warren, Jerome I. Rotter, Nathan A. Bihlmeyer, Man Li, Jeffrey Haessler, Charles Kooperberg, Moritz F. Sinner, Sean J. Jurgens, Folkert W. Asselbergs, Dan E. Arking, Ruifang Li-Gao, Jessica van Setten, Patricia B. Munroe, Jørgen K. Kanters, Stefan Kääb, Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Erasmus MC other, Medical Informatics, Internal Medicine, Epidemiology, and Cardiology
- Subjects
0301 basic medicine ,PROTEIN ,population ,030204 cardiovascular system & hematology ,Cardiovascular ,Electrocardiography ,0302 clinical medicine ,MYH6 ,Atrial Fibrillation ,2.1 Biological and endogenous factors ,Connectin ,atrial fibrillation ,Aetiology ,Exome ,MYOSIN HEAVY-CHAIN ,RISK ,education.field_of_study ,NAV1.8 Voltage-Gated Sodium Channel/genetics ,Connectin/genetics ,Atrial fibrillation ,General Medicine ,ASSOCIATION ,Heart Disease ,Duration (music) ,Cardiology ,EXPRESSION ,medicine.medical_specialty ,HMGA2 ,Population ,INDEXES ,Quantitative Trait Loci ,Transcription Factors/genetics ,Electrophysiology ,Genetic ,Genome-wide Association Studies ,Article ,NAV1.8 Voltage-Gated Sodium Channel ,03 medical and health sciences ,Myosin Heavy Chains/genetics ,Clinical Research ,Internal medicine ,Cardiac conduction ,Cardiac Myosins/genetics ,P wave duration ,medicine ,Genetics ,Humans ,education ,RECURRENCE ,Homeodomain Proteins ,Myosin Heavy Chains ,business.industry ,Human Genome ,Genetic Variation ,medicine.disease ,electrophysiology ,Atrial Fibrillation/ethnology ,030104 developmental biology ,genome-wide association studies ,Homeodomain Proteins/genetics ,genetic ,business ,Cardiac Myosins ,exome ,Transcription Factors ,Genome-Wide Association Study - Abstract
Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci ( TTN , CAND2 , SCN10A , PITX2 , CAV1 , SYNPO2L , SOX5 , TBX5, MYH6, RPL3L ). The top variants at known sarcomere genes ( TTN, MYH6 ) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A ) were associated with longer PWD but lower AF risk. Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
- Published
- 2020