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

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 10,000 individuals and followed up the top signals in an additional 10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 × 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 × 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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Acknowledgements

The authors would like to thank the individuals that participated in the study and whose contribution made this work possible. We thank our valued colleagues who contributed to the data collection, sample handling, genotyping and data analysis.

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The study was designed and results interpreted by H.H., D.F.G., D.O.A., A.J., U.T. and K.S. Statistical analysis was carried out by D.F.G., S.A.G., G. Thorleifsson and A.K. D.O.A., G. Thorgeirsson. and H.S. collected the Icelandic data. E.B.M., I.N., A.N., T.W., E.M.H., K.H., C.S. and M.-L.L. collected the Norwegian data. Authors H.H., D.F.G., D.O.A., U.T. and K.S. wrote the first draft of the paper. All authors contributed to the final version.

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Correspondence to Hilma Holm or Kari Stefansson.

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Competing interests

H.H., D.F.G., G.Thorleifsson, A.J., S.A.G., U.T. and K.S. are employees of and/or own stock in deCODE Genetics Inc.

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Holm, H., Gudbjartsson, D., Arnar, D. et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet 42, 117–122 (2010). https://doi.org/10.1038/ng.511

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