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.
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通过对 38,384 名冰岛人进行 SNP 基因分型、全基因组测序和插补的互补应用，我们发现了一种以前未被识别的病态窦房结综合征易感基因 MYH6，它编码心肌肌球蛋白的 α 重链亚基。该基因中的错义变异 c.2161C>T 导致概念性氨基酸取代 p.Arg721Trp，在冰岛人中的等位基因频率为 0.38%，与病态窦房结综合征相关，比值比 = 1 2.53，P = 1.5 × 10−29。我们发现，对于 c.2161C>T 变体非携带者来说，被诊断为病态窦房结综合征的终生风险约为 6%，而对于 c.2161C>T 变体携带者来说，这一风险约为 50%。
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 = 1 2.53 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.