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

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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
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Issue Date
2010-02-01

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Citation
Nat. Genet. 2010, 42(2):117-22
Abstract
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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http://dx.doi.org/10.1038/ng.511
ae974a485f413a2113503eed53cd6c53
10.1038/ng.511
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