@article{f08d1b7382aa43bc9712b420e5443765,
title = "Burden of rare sarcomere gene variants in the framingham and jackson heart study cohorts",
abstract = "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.",
author = "Bick, {Alexander G.} and Jason Flannick and Kaoru Ito and Susan Cheng and Vasan, {Ramachandran S.} and Parfenov, {Michael G.} and Herman, {Daniel S.} and Depalma, {Steven R.} and Namrata Gupta and Gabriel, {Stacey B.} and Funke, {Birgit H.} and Rehm, {Heidi L.} and Benjamin, {Emelia J.} and Jayashri Aragam and Taylor, {Herman A.} and Fox, {Ervin R.} and Christopher Newton-Cheh and Sekar Kathiresan and O'donnell, {Christopher J.} and Wilson, {James G.} and Altshuler, {David M.} and Hirschhorn, {Joel N.} and Seidman, {J. G.} and Christine Seidman",
note = "Funding Information: We gratefully acknowledge the contribution of Framingham and Jackson Heart Study cohort participants. This work was supported by grants from the National Human Genome Research Institute (Medical Sequencing Program grant U54 HG003067, to the Broad Institute PI, Lander), the National Heart, Lung and Blood Institute (HL080494-05 to C.E.S. and J.G.S.), and the Howard Hughes Medical Institute (to C.E.S). A.G.B. and D.S.H. are supported by NIH Medical Scientist Training Program fellowship 5T32GM007753-33. S.C. is supported in part by grant K99HL107642 and the Ellison Foundation. The Jackson Heart Study is supported by contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the National Heart, Lung, and Blood Institute, the National Institute for Minority Health and Health Disparities, and additional support from the National Institute of Biomedical Imaging and Bioengineering. The Framingham Heart Study was supported by contracts N01-HC-25195 and 6R01-NS 17950 from the National Heart, Lung and Blood Institute and genotyping services from Affymetrix, Inc. (contract No. N02-HL-6-4278 for the SNP Health Association Resource [SHARe] project). ",
year = "2012",
month = sep,
day = "7",
doi = "10.1016/j.ajhg.2012.07.017",
language = "English (US)",
volume = "91",
pages = "513--519",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",
}