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

作者：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 Guomundur; Jonasdottir Aslaug; Sigurdsson Asgeir; Stefansson Hreinn; Werge Thomas; Rafnar Thorunn; Kiemeney Lambertus A; Parvez Babar; Muhammad Raafia; Roden Dan M; Darbar Dawood; Thorleifsson Gudmar

来源：Nature Genetics, 2011, 43(4): 316-U148.

DOI：10.1038/ng.781

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 x 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.

• 出版日期2011-4
• 单位上海市精神卫生中心