A rare variant in MYH6 is associated with high risk of sick sinus syndrome by Holm Hilma, Gudbjartsson Daniel F, Sulem Patrick, Masson Gisli, Helgadottir Hafdis Th, Zanon Carlo, Magnusson Olafur Th, Helgason Agnar, Saemundsdottir Jona, Gylfason Arnaldur, Stefansdottir Hrafnhildur, Gretarsdottir Solveig, Matthiasson Stefan E, Thorgeirsson Gu Mundur, Jonasdottir Aslaug, Sigurdsson Asgeir, Stefansson Hreinn, Werge Thomas, Rafnar Thorunn, Kiemeney Lambertus A, Parvez Babar, Muhammad Raafia, Roden Dan M, Darbar Dawood, Thorleifsson Gudmar, Walters G Bragi, Kong Augustine, Thorsteinsdottir Unnur, Arnar David O, Stefansson Kari in Nature genetics (2011). PubMed


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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