Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval
| Autor: | Tamara B. Harris, Niels Grarup, Marcus Dörr, Martina Müller-Nurasyid, Torben Hansen, Lu-Chen Weng, Honghuang Lin, Thibaud Boutin, Joshua C. Bis, Farid Radmanesh, Jie Yao, Nilesh J. Samani, Ozren Polašek, Massimo Mangino, Charles Kooperberg, Vilmundur Gudnason, Stephan B. Felix, Bruno H. Stricker, Elsayed Z. Soliman, Nathan A. Bihlmeyer, Jette Bork-Jensen, Dan E. Arking, J. Marten, Mika Kähönen, Kenneth Rice, Nona Sotoodehnia, Heather Jameson, Henry J. Lin, Jørgen K. Kanters, Jared W. Magnani, Mark Eijgelsheim, Hao Mei, Tim D. Spector, Oluf Pedersen, Allan Linneberg, G. Homuth, Chengping Wen, Olli T. Raitakari, Blair H. Smith, Marco V Perez, Melanie Waldenberger, Bram P. Prins, James G. Wilson, Xiuqing Guo, Sandosh Padmanabhan, Peter van der Meer, Stefan Weiss, Leo-Pekka Lyytikäinen, Colleen M. Sitlani, Alvaro Alonso, Leanne M. Hall, Cornelia M. van Duijn, Jessica van Setten, Helen R. Warren, Kent D. Taylor, Niek Verweij, Man Li, Moritz F. Sinner, Igor Rudan, Christopher P. Nelson, Emelia J. Benjamin, William J. Hucker, Marten E. van den Berg, Alan Hanley, Jerome I. Rotter, D. O. Mook-Kanamori, Susan R. Heckbert, Bruce M. Psaty, Caroline Hayward, Yalda Jamshidi, Patrick T. Ellinor, John M. C. Connell, Patricia B. Munroe, Lenore J. Launer, Stefan Kääb, Uwe Völker, Ruifang Li-Gao, Jan A. Kors, Annette Peters, J. Wouter Jukema, Jeffrey Haessler, Aaron Isaacs, Folkert W. Asselbergs, Rudolf A. de Boer, Konstantin Strauch, Albert V. Smith, Jonathan Rosand, Steven A. Lubitz, F. Rivadeneira, Nathan R. Tucker, Michiel L. Bots, Zhijun Xie, Jennifer A. Brody, Stella Trompet, Thomas Meitinger, André G. Uitterlinden, Pim van der Harst, Paul L. Huang, Henry Völzke, Terho Lehtimäki, Yii-Der Ida Chen |
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| Přispěvatelé: | Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Epidemiology, Medical Informatics, Clinical Chemistry, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AII - Infectious diseases, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Amsterdam institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Intensive Care Medicine, Experimental Immunology, Radiotherapy, Graduate School, Cardiology, Biochemie, RS: CARIM - R1.01 - Blood proteins & engineering, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, RS: FHML MaCSBio |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine SCN10A Heart morphogenesis Quantitative Trait Loci LOCI Locus (genetics) Genome-wide association study atrioventricular node SUSCEPTIBILITY Regulatory Sequences Nucleic Acid 030204 cardiovascular system & hematology Quantitative trait locus Biology VARIANTS Atrioventricular Node Genetic Loci Genome-wide Association Study Article genome-wide 03 medical and health sciences Electrocardiography 0302 clinical medicine Genetic variation Humans Genetic Predisposition to Disease PR interval GENOME-WIDE ASSOCIATION SCN5A GENE Aged Genetic association Genetics genome-wide association study HERITABILITY MUTATIONS Genetic Variation genetic loci General Medicine Middle Aged ta3121 Heritability DILATED CARDIOMYOPATHY 030104 developmental biology LONG QT SYNDROME CONDUCTION ATRIAL-FIBRILLATION Female QRS DURATION SUDDEN CARDIAC DEATH |
| Zdroj: | Circulation. Genomic and precision medicine, 11(5):002037. LIPPINCOTT WILLIAMS & WILKINS Circulation: Genomic and Precision Medicine, 11(5) Circulation. Genomic and precision medicine, 11(5), e002037. Lippincott Williams and Wilkins Ltd. Circulation-Genomic and Precision Medicine, 11(5):UNSP e002037. Lippincott Williams & Wilkins Circulation. Genomic and precision medicine, 11(5). Lippincott Williams and Wilkins Ltd. Circ. Genom. Precis. Med. 11:e002037 (2018) Circulation: Genomic and Precision Medicine, 11(5):e002037 . Lippincott Williams and Wilkins Ltd. Lin, H, van Setten, J, Smith, A V, Bihlmeyer, N A, Warren, H, Brody, J, Radmanesh, F, Hall, L M, Grarup, N, Müller-Nurasyid, M & Rudan, I 2018, ' Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval ', Circulation: Genomic and Precision Medicine . https://doi.org/10.1161/CIRCGEN.117.002037 |
| ISSN: | 2574-8300 1942-325X |
| DOI: | 10.1161/circgen.117.002037 |
| Popis: | 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 −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. |
| Databáze: | OpenAIRE |
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