Scientific Publications

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

Publication TypeJournal Article
AuthorsBick, AG, Flannick J., Ito K., Cheng S., Vasan RS, Parfenov MG, Herman DS, Depalma SR, Gupta N., Gabriel SB, Funke BH, Rehm HL, Benjamin EJ, Aragam J., Taylor HA Jr, Fox ER, Newton-Cheh C., Kathiresan S., O'Donnell CJ, Wilson JG, Altshuler DM, Hirschhorn JN, Seidman JG, and Seidman C.
AbstractRare 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.
Year of Publication2012
JournalAmerican journal of human genetics
Volume91
Issue3
Pages513-9
Date Published (YYYY/MM/DD)2012/09/07
ISSN Number0002-9297
DOI10.1016/j.ajhg.2012.07.017
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/22958901?dopt=Abstract