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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiac Myosins / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Heart Diseases / genetics
  • Heart Rate / genetics
  • Heterozygote
  • Humans
  • Iceland
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Myosin Heavy Chains / genetics*
  • Odds Ratio
  • Oligonucleotide Array Sequence Analysis
  • Penetrance
  • Polymorphism, Single Nucleotide
  • Sick Sinus Syndrome / genetics*
  • Sick Sinus Syndrome / physiopathology

Substances

  • MYH6 protein, human
  • Cardiac Myosins
  • Myosin Heavy Chains