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

被引：111

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

共 27 条

[1] Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension
Brown, DW
Giles, WH
Croft, JB
[J]. AMERICAN HEART JOURNAL, 2000, 140 (06) : 848 - 856
[2] IMPROVED SEX-SPECIFIC CRITERIA OF LEFT-VENTRICULAR HYPERTROPHY FOR CLINICAL AND COMPUTER INTERPRETATION OF ELECTROCARDIOGRAMS - VALIDATION WITH AUTOPSY FINDINGS
CASALE, PN
DEVEREUX, RB
ALONSO, DR
CAMPO, E
KLIGFIELD, P
[J]. CIRCULATION, 1987, 75 (03) : 565 - 572
[3] General cardiovascular risk profile for use in primary care - The Framingham Heart Study
D'Agostino, Ralph B.
Vasan, Ramachandran S.
Pencina, Michael J.
Wolf, Philip A.
Cobain, Mark
Massaro, Joseph M.
Kannel, William B.
[J]. CIRCULATION, 2008, 117 (06) : 743 - 753
[4] Association of left ventricular hypertrophy with metabolic risk factors: the HyperGEN study
de Simone, G
Palmieri, V
Bella, JN
Celentano, A
Hong, YL
Oberman, A
Kitzman, DW
Hopkins, PN
Arnett, DK
Devereux, RB
[J]. JOURNAL OF HYPERTENSION, 2002, 20 (02) : 323 - 331
[5] A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, Mark A.
Banks, Eric
Poplin, Ryan
Garimella, Kiran V.
Maguire, Jared R.
Hartl, Christopher
Philippakis, Anthony A.
del Angel, Guillermo
Rivas, Manuel A.
Hanna, Matt
McKenna, Aaron
Fennell, Tim J.
Kernytsky, Andrew M.
Sivachenko, Andrey Y.
Cibulskis, Kristian
Gabriel, Stacey B.
Altshuler, David
Daly, Mark J.
[J]. NATURE GENETICS, 2011, 43 (05) : 491 - +
[6] DEVEREUX RB, 1987, HYPERTENSION, V9, P53
[7] The pathogenesis of familial hypertrophic cardiomyopathy:: Early and evolving effects from an α-cardiac myosin heavy chain missense mutation
Georgakopoulos, D
Christe, ME
Giewat, M
Seidman, CM
Seidman, JG
Kass, DA
[J]. NATURE MEDICINE, 1999, 5 (03) : 327 - 330
[8] Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing
Gnirke, Andreas
Melnikov, Alexandre
Maguire, Jared
Rogov, Peter
LeProust, Emily M.
Brockman, William
Fennell, Timothy
Giannoukos, Georgia
Fisher, Sheila
Russ, Carsten
Gabriel, Stacey
Jaffe, David B.
Lander, Eric S.
Nusbaum, Chad
[J]. NATURE BIOTECHNOLOGY, 2009, 27 (02) : 182 - 189
[9] Genetics of the Framingham Heart Study Population
Govindaraju, Diddahally R.
Cupples, L. Adrienne
Kannel, William B.
O'Donnell, Christopher J.
Atwood, Larry D.
D'Agostino, Ralph B., Sr.
Fox, Caroline S.
Larson, Marty
Levy, Daniel
Murabito, Joanne
Vasan, Ramachandran S.
Splansky, Greta Lee
Wolf, Philip A.
Benjamin, Emelia J.
[J]. ADVANCES IN GENETICS, VOL 62, 2008, 62 : 33 - 65
[10] A PROGNOSTIC COMPARISON OF ASYMPTOMATIC LEFT-VENTRICULAR HYPERTROPHY AND UNRECOGNIZED MYOCARDIAL-INFARCTION - THE FRAMINGHAM-STUDY
KANNEL, WB
ABBOTT, RD
[J]. AMERICAN HEART JOURNAL, 1986, 111 (02) : 391 - 397

← 1 2 3 →