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American journal of human genetics DOI:10.1016/j.ajhg.2012.07.017

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

Publication TypeJournal Article
Year of Publication2012
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, J, Fox, ER, Newton-Cheh, C, Kathiresan, S, O'Donnell, CJ, Wilson, JG, Altshuler, DM, Hirschhorn, JN, Seidman, JG, Seidman, C
JournalAmerican journal of human genetics
Date Published2012/09/07

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.