A rare variant in MYH6 is associated with high risk of sick sinus syndrome PMID: 21378987

Target-related Cytokines

2026-09-23

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

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.