2. Academic Validation
  3. A rare variant in MYH6 is associated with high risk of sick sinus syndrome

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

  • Nat Genet. 2011 Mar 6;43(4):316-20. doi: 10.1038/ng.781.
Hilma Holm 1,  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,  Gu Mundur 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
Affiliations

Affiliation

  • 1 deCODE Genetics, Sturlugata 8, Reykjavik, Iceland. hilma.holm@decode.is
PMID: 21378987 DOI: 10.1038/ng.781
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.

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