Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1

被引：157

作者：

LeMaire, Scott A. ^{[2
]}

McDonald, Merry-Lynn N. ^{[3
]}

Guo, Dong-chuan ^{[1
]}

Russell, Ludivine ^{[2
]}

Miller, Charles C., III ^{[4
]}

Johnson, Ralph J. ^{[1
]}

Bekheirnia, Mir Reza ^{[3
]}

Franco, Luis M. ^{[3
]}

Nguyen, Mary ^{[2
]}

Pyeritz, Reed E. ^{[5
]}

Bavaria, Joseph E. ^{[6
]}

Devereux, Richard ^{[7
]}

Maslen, Cheryl ^{[8
]}

Holmes, Kathryn W. ^{[9
]}

Eagle, Kim ^{[10
]}

Body, Simon C. ^{[11
]}

Seidman, Christine ^{[12
]}

Seidman, J. G. ^{[12
]}

Isselbacher, Eric M. ^{[13
]}

Bray, Molly ^{[14
]}

Coselli, Joseph S. ^{[2
]}

Estrera, Anthony L. ^{[4
]}

Safi, Hazim J. ^{[4
]}

Belmont, John W. ^{[3
]}

Leal, Suzanne M. ^{[3
]}

Milewicz, Dianna M. ^{[1
,15
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Div Med Genet, Dept Internal Med, Houston, TX USA

[2] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[4] Univ Texas Hlth Sci Ctr Houston, Dept Cardiothorac & Vasc Surg, Houston, TX USA

[5] Univ Penn, Dept Med, Div Med Genet, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Surg, Div Cardiovasc Surg, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Weill Cornell Med Coll, Dept Med, Greenberg Div Cardiol, New York, NY USA

[8] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Dept Mol & Med Genet, Portland, OR 97201 USA

[9] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[10] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA

[11] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA

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

[13] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[14] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[15] St Lukes Episcopal Hosp, Texas Heart Inst, Med Serv, Houston, TX USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

美国国家卫生研究院;

关键词：

MARFAN-SYNDROME; MOUSE MODEL; MUTATIONS; DISEASE; VALVE; ADULTS;

D O I：

10.1038/ng.934

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 x 10(-5) in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD.

引用

页码：996 / U109

页数：7

共 27 条

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