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Am J Hum Genet 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, Fox, ER, Newton-Cheh, C, Kathiresan, S, O'Donnell, CJ, Wilson, JG, Altshuler, DM, Hirschhorn, JN, Seidman, JG, Seidman, C
JournalAm J Hum Genet
Volume91
Issue3
Pages513-9
Date Published2012 Sep 07
ISSN1537-6605
KeywordsAdult, Aged, Aged, 80 and over, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Cardiovascular Diseases, Cohort Studies, Female, Genetic Variation, Humans, Male, Middle Aged, Models, Cardiovascular, Risk Factors, Sarcomeres
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0002-9297(12)00374-6
DOI10.1016/j.ajhg.2012.07.017
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22958901?dopt=Abstract

Alternate JournalAm. J. Hum. Genet.
PubMed ID22958901
PubMed Central IDPMC3511985
Grant ListN02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
K99HL107642 / HL / NHLBI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 HL080494 / HL / NHLBI NIH HHS / United States
5T32GM007753-33 / GM / NIGMS NIH HHS / United States
N01HC95170 / HL / NHLBI NIH HHS / United States
N01-HC-95171 / HC / NHLBI NIH HHS / United States
6R01-NS 17950 / NS / NINDS NIH HHS / United States
N01-HC-95172 / HC / NHLBI NIH HHS / United States
N01HC95171 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HL080494-05 / HL / NHLBI NIH HHS / United States
N01-HC-95170 / HC / NHLBI NIH HHS / United States
K99 HL107642 / HL / NHLBI NIH HHS / United States
N01HC95172 / HL / NHLBI NIH HHS / United States