Several common variants modulate heart rate, PR interval and QRS duration

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in indi...

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Bibliographic Details
Published in:Nature Genetics
Main Authors: Holm, Hilma, Gudbjartsson, Daniel F, Arnar, David O, Thorleifsson, Gudmar, Thorgeirsson, Gudmundur, Stefansdottir, Hrafnhildur, Gudjonsson, Sigurjon A, Jonasdottir, Aslaug, Mathiesen, Ellisiv B, Njølstad, Inger, Nyrnes, Audhild, Wilsgaard, Tom, Hald, Erin M, Hveem, Kristian, Stoltenberg, Camilla, Løchen, Maja-Lisa, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari
Other Authors: deCODE genetics, Reykjavik, Iceland. hilma.holm@decode.is
Format: Article in Journal/Newspaper
Language:English
Published: Nature Pub. Co. 2010
Subjects:
Aged
Arrhythmias
Cardiac
Atrial Fibrillation
Atrioventricular Block
Cardiac Myosins
Electrocardiography
Female
Genetic Loci
Genetic Variation
Genome-Wide Association Study
Heart Conduction System
Heart Rate
Iceland
Inheritance Patterns
Male
Middle Aged
Myosin Heavy Chains
Pacemaker
Artificial
Reproducibility of Results
Sick Sinus Syndrome
Online Access:http://hdl.handle.net/2336/96605
https://doi.org/10.1038/ng.511
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Summary:To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in approximately 10,000 individuals and followed up the top signals in an additional approximately 10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 x 10(-7)). We identified one locus for heart rate (MYH6), four for PR interval (TBX5, SCN10A, CAV1 and ARHGAP24) and four for QRS duration (TBX5, SCN10A, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between TBX5 and CAV1 and atrial fibrillation (P = 4.0 x 10(-5) and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval.

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