Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts

被引：112

作者：

Bick, Alexander G. ^{[1
,2
]}

Flannick, Jason ^{[2
,3
]}

Ito, Kaoru ^{[1
]}

Cheng, Susan ^{[4
]}

Vasan, Ramachandran S. ^{[5
,6
,7
]}

Parfenov, Michael G. ^{[1
]}

Herman, Daniel S. ^{[1
]}

DePalma, Steven R. ^{[1
]}

Gupta, Namrata ^{[2
]}

Gabriel, Stacey B. ^{[2
]}

Funke, Birgit H. ^{[8
,18
]}

Rehm, Heidi L. ^{[8
,18
]}

Benjamin, Emelia J. ^{[5
,6
,7
,9
]}

Aragam, Jayashri ^{[4
]}

Taylor, Herman A., Jr. ^{[10
,11
,19
]}

Fox, Ervin R. ^{[10
]}

Newton-Cheh, Christopher ^{[3
,5
,12
]}

Kathiresan, Sekar ^{[3
,5
,12
]}

O'Donnell, Christopher J. ^{[5
,13
]}

Wilson, James G. ^{[14
]}

Altshuler, David M. ^{[2
,3
]}

Hirschhorn, Joel N. ^{[1
,2
,15
,16
,17
]}

Seidman, J. G. ^{[1
]}

Seidman, Christine ^{[1
,4
,20
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA

[5] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[6] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA

[7] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA

[8] Partners Ctr Personalized Genet Med, Lab Mol Med, Cambridge, MA 02139 USA

[9] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA

[10] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

[11] Jackson State Univ, Jackson, MS 39217 USA

[12] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[13] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[14] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

[15] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[16] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[17] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[18] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[19] Tougaloo Coll, Tougaloo, MS 39174 USA

[20] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 91卷 / 03期

关键词：

LEFT-VENTRICULAR HYPERTROPHY; RISK; MASS; CARDIOMYOPATHY; ASSOCIATION; DISEASE; PROFILE;

D O I：

10.1016/j.ajhg.2012.07.017

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：513 / 519

页数：7

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