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

2011; Nature Portfolio; Volume: 43; Issue: 4 Linguagem: Inglês

10.1038/ng.781

1546-1718

Hilma Hólm, Daníel F. Guðbjartsson, Patrick Sulem, Gísli Másson, Hafdís T. Helgadóttir, Carlo Zanon, Ólafur Þ. Magnússon, Agnar Helgason, Jona Saemundsdottir, Arnaldur Gylfason, Hrafnhildur Stefansdottir, Sólveig Grétarsdóttir, Stefán E. Matthíasson, Gu∂mundur Thorgeirsson, Áslaug Jónasdóttir, Ásgeir Sigurðsson, Hreinn Stefánsson, Thomas Werge, Þórunn Rafnar, Lambertus A. Kiemeney, Babar Parvez, Raafia Muhammad, Dan M. Roden, Dawood Darbar, Guðmar Þorleifsson, G. Bragi Walters, Augustine Kong, Unnur Þorsteinsdóttir, Davíð O. Arnar, Kāri Stefánsson,

Whipple's Disease and Interleukins

Hilma Holm et al. report a rare missense variant MYH6 that is associated with a high risk of sick sinus syndrome in Icelanders. This heart condition is found most often in elderly people and is the most frequent reason a heart pacemaker is implanted. 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.