A rare variant in MYH6 is associated with high risk of sick sinus syndrome

Hilma Holm; Daniel F. Gudbjartsson; Patrick Sulem; Gisli Masson; Hafdis Th Helgadottir; Carlo Zanon; Olafur Th Magnusson; Agnar Helgason; Jona Saemundsdottir; Arnaldur Gylfason; Hrafnhildur Stefansdottir; Solveig Gretarsdottir; Stefan E. Matthiasson; Guomundur Thorgeirsson; Aslaug Jonasdottir; Asgeir Sigurdsson; Hreinn Stefansson; Thomas Werge; Thorunn Rafnar; Lambertus A. Kiemeney; Babar Parvez; Raafia Muhammad; Dan M. Roden; Dawood Darbar; Gudmar Thorleifsson; G. Bragi Walters; Augustine Kong; Unnur Thorsteinsdottir; David O. Arnar; Kari Stefansson

doi:10.1038/ng.781

A rare variant in MYH6 is associated with high risk of sick sinus syndrome

Hilma Holm
, Daniel F. Gudbjartsson
, Patrick Sulem
, Gisli Masson
, Hafdis Th Helgadottir
, Carlo Zanon
, Olafur Th Magnusson
, Agnar Helgason
, Jona Saemundsdottir
, Arnaldur Gylfason
, Hrafnhildur Stefansdottir
, Solveig Gretarsdottir
, Stefan E. Matthiasson
, Guomundur Thorgeirsson
, Aslaug Jonasdottir
, Asgeir Sigurdsson
, Hreinn Stefansson
, Thomas Werge
, Thorunn Rafnar
, Lambertus A. Kiemeney

Babar Parvez, Raafia Muhammad, Dan M. Roden, Dawood Darbar, Gudmar Thorleifsson, G. Bragi Walters, Augustine Kong, Unnur Thorsteinsdottir, David O. Arnar, Kari Stefansson

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

267 Scopus citations

Abstract

Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5^-10'29. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant.

Original language	English (US)
Pages (from-to)	316-323
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	4
DOIs	https://doi.org/10.1038/ng.781
State	Published - Feb 2011

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.781

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Holm, H., Gudbjartsson, D. F., Sulem, P., Masson, G., Helgadottir, H. T., Zanon, C., Magnusson, O. T., Helgason, A., Saemundsdottir, J., Gylfason, A., Stefansdottir, H., Gretarsdottir, S., Matthiasson, S. E., Thorgeirsson, G., Jonasdottir, A., Sigurdsson, A., Stefansson, H., Werge, T., Rafnar, T., ... Stefansson, K. (2011). A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nature Genetics, 43(4), 316-323. https://doi.org/10.1038/ng.781

@article{d7774c56b2824d9fafb442a493309101,

title = "A rare variant in MYH6 is associated with high risk of sick sinus syndrome",

abstract = "Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38\% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5-10'29. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6\% for non-carriers of c.2161C>T but is approximately 50\% for carriers of the c.2161C>T variant.",

author = "Hilma Holm and Gudbjartsson, \{Daniel F.\} and Patrick Sulem and Gisli Masson and Helgadottir, \{Hafdis Th\} and Carlo Zanon and Magnusson, \{Olafur Th\} and Agnar Helgason and Jona Saemundsdottir and Arnaldur Gylfason and Hrafnhildur Stefansdottir and Solveig Gretarsdottir and Matthiasson, \{Stefan E.\} and Guomundur Thorgeirsson and Aslaug Jonasdottir and Asgeir Sigurdsson and Hreinn Stefansson and Thomas Werge and Thorunn Rafnar and Kiemeney, \{Lambertus A.\} and Babar Parvez and Raafia Muhammad and Roden, \{Dan M.\} and Dawood Darbar and Gudmar Thorleifsson and Walters, \{G. Bragi\} and Augustine Kong and Unnur Thorsteinsdottir and Arnar, \{David O.\} and Kari Stefansson",

year = "2011",

month = feb,

doi = "10.1038/ng.781",

language = "English (US)",

volume = "43",

pages = "316--323",

journal = "Nature Genetics",

issn = "1061-4036",

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Holm, H, Gudbjartsson, DF, Sulem, P, Masson, G, Helgadottir, HT, Zanon, C, Magnusson, OT, Helgason, A, Saemundsdottir, J, Gylfason, A, Stefansdottir, H, Gretarsdottir, S, Matthiasson, SE, Thorgeirsson, G, Jonasdottir, A, Sigurdsson, A, Stefansson, H, Werge, T, Rafnar, T, Kiemeney, LA, Parvez, B, Muhammad, R, Roden, DM, Darbar, D, Thorleifsson, G, Walters, GB, Kong, A, Thorsteinsdottir, U, Arnar, DO & Stefansson, K 2011, 'A rare variant in MYH6 is associated with high risk of sick sinus syndrome', Nature Genetics, vol. 43, no. 4, pp. 316-323. https://doi.org/10.1038/ng.781

TY - JOUR

T1 - A rare variant in MYH6 is associated with high risk of sick sinus syndrome

AU - Holm, Hilma

AU - Gudbjartsson, Daniel F.

AU - Sulem, Patrick

AU - Masson, Gisli

AU - Helgadottir, Hafdis Th

AU - Zanon, Carlo

AU - Magnusson, Olafur Th

AU - Helgason, Agnar

AU - Saemundsdottir, Jona

AU - Gylfason, Arnaldur

AU - Stefansdottir, Hrafnhildur

AU - Gretarsdottir, Solveig

AU - Matthiasson, Stefan E.

AU - Thorgeirsson, Guomundur

AU - Jonasdottir, Aslaug

AU - Sigurdsson, Asgeir

AU - Stefansson, Hreinn

AU - Werge, Thomas

AU - Rafnar, Thorunn

AU - Kiemeney, Lambertus A.

AU - Parvez, Babar

AU - Muhammad, Raafia

AU - Roden, Dan M.

AU - Darbar, Dawood

AU - Thorleifsson, Gudmar

AU - Walters, G. Bragi

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Arnar, David O.

AU - Stefansson, Kari

PY - 2011/2

Y1 - 2011/2

N2 - Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5-10'29. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant.

AB - Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5-10'29. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant.

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U2 - 10.1038/ng.781

DO - 10.1038/ng.781

M3 - Article

C2 - 21378987

AN - SCOPUS:79953212557

SN - 1061-4036

VL - 43

SP - 316

EP - 323

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

A rare variant in MYH6 is associated with high risk of sick sinus syndrome

Abstract

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