Sequence variants with large effects on cardiac electrophysiology and disease

Kristjan Norland; Gardar Sveinbjornsson; Rosa B. Thorolfsdottir; Olafur B. Davidsson; Vinicius Tragante; Sridharan Rajamani; Anna Helgadottir; Solveig Gretarsdottir; Jessica van Setten; Folkert W. Asselbergs; Jon Th Sverrisson; Sigurdur S. Stephensen; Gylfi Oskarsson; Emil L. Sigurdsson; Karl Andersen; Ragnar Danielsen; Gudmundur Thorgeirsson; Unnur Thorsteinsdottir; David O. Arnar; Patrick Sulem; Hilma Holm; Daniel F. Gudbjartsson; Kari Stefansson

doi:10.1038/s41467-019-12682-9

Sequence variants with large effects on cardiac electrophysiology and disease

Kristjan Norland, Gardar Sveinbjornsson, Rosa B. Thorolfsdottir, Olafur B. Davidsson, Vinicius Tragante, Sridharan Rajamani, Anna Helgadottir, Solveig Gretarsdottir, Jessica van Setten, Folkert W. Asselbergs, Jon Th Sverrisson, Sigurdur S. Stephensen, Gylfi Oskarsson, Emil L. Sigurdsson, Karl Andersen, Ragnar Danielsen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, David O. Arnar, Patrick SulemHilma Holm, Daniel F. Gudbjartsson^*, Kari Stefansson

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

Original language	English
Article number	4803
Number of pages	10
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12682-9
Publication status	Published - 1 Dec 2019

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Norland, K., Sveinbjornsson, G., Thorolfsdottir, R. B., Davidsson, O. B., Tragante, V., Rajamani, S., Helgadottir, A., Gretarsdottir, S., van Setten, J., Asselbergs, F. W., Sverrisson, J. T., Stephensen, S. S., Oskarsson, G., Sigurdsson, E. L., Andersen, K., Danielsen, R., Thorgeirsson, G., Thorsteinsdottir, U., Arnar, D. O., ... Stefansson, K. (2019). Sequence variants with large effects on cardiac electrophysiology and disease. Nature Communications, 10(1), Article 4803. https://doi.org/10.1038/s41467-019-12682-9

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title = "Sequence variants with large effects on cardiac electrophysiology and disease",

abstract = "Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.",

author = "Kristjan Norland and Gardar Sveinbjornsson and Thorolfsdottir, {Rosa B.} and Davidsson, {Olafur B.} and Vinicius Tragante and Sridharan Rajamani and Anna Helgadottir and Solveig Gretarsdottir and {van Setten}, Jessica and Asselbergs, {Folkert W.} and Sverrisson, {Jon Th} and Stephensen, {Sigurdur S.} and Gylfi Oskarsson and Sigurdsson, {Emil L.} and Karl Andersen and Ragnar Danielsen and Gudmundur Thorgeirsson and Unnur Thorsteinsdottir and Arnar, {David O.} and Patrick Sulem and Hilma Holm and Gudbjartsson, {Daniel F.} and Kari Stefansson",

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doi = "10.1038/s41467-019-12682-9",

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Norland, K, Sveinbjornsson, G, Thorolfsdottir, RB, Davidsson, OB, Tragante, V, Rajamani, S, Helgadottir, A, Gretarsdottir, S, van Setten, J , Asselbergs, FW, Sverrisson, JT, Stephensen, SS, Oskarsson, G, Sigurdsson, EL, Andersen, K, Danielsen, R, Thorgeirsson, G, Thorsteinsdottir, U, Arnar, DO, Sulem, P, Holm, H, Gudbjartsson, DF & Stefansson, K 2019, 'Sequence variants with large effects on cardiac electrophysiology and disease', Nature Communications, vol. 10, no. 1, 4803. https://doi.org/10.1038/s41467-019-12682-9

TY - JOUR

T1 - Sequence variants with large effects on cardiac electrophysiology and disease

AU - Norland, Kristjan

AU - Sveinbjornsson, Gardar

AU - Thorolfsdottir, Rosa B.

AU - Davidsson, Olafur B.

AU - Tragante, Vinicius

AU - Rajamani, Sridharan

AU - Helgadottir, Anna

AU - Gretarsdottir, Solveig

AU - van Setten, Jessica

AU - Asselbergs, Folkert W.

AU - Sverrisson, Jon Th

AU - Stephensen, Sigurdur S.

AU - Oskarsson, Gylfi

AU - Sigurdsson, Emil L.

AU - Andersen, Karl

AU - Danielsen, Ragnar

AU - Thorgeirsson, Gudmundur

AU - Thorsteinsdottir, Unnur

AU - Arnar, David O.

AU - Sulem, Patrick

AU - Holm, Hilma

AU - Gudbjartsson, Daniel F.

AU - Stefansson, Kari

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

AB - Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

UR - http://www.scopus.com/inward/record.url?scp=85073726304&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-12682-9

DO - 10.1038/s41467-019-12682-9

M3 - Article

C2 - 31641117

AN - SCOPUS:85073726304

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4803

ER -

Sequence variants with large effects on cardiac electrophysiology and disease

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