Burden of rare sarcomere gene variants in the framingham and jackson heart study cohorts

Alexander G. Bick, Jason Flannick, Kaoru Ito, Susan Cheng, Ramachandran S. Vasan, Michael G. Parfenov, Daniel S. Herman, Steven R. Depalma, Namrata Gupta, Stacey B. Gabriel, Birgit H. Funke, Heidi L. Rehm, Emelia J. Benjamin, Jayashri Aragam, Herman A. Taylor, Ervin R. Fox, Christopher Newton-Cheh, Sekar Kathiresan, Christopher J. O'donnell, James G. WilsonDavid M. Altshuler, Joel N. Hirschhorn, J. G. Seidman, Christine Seidman

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis.

Original languageEnglish (US)
Pages (from-to)513-519
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - Sep 7 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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