The Congenital Heart Disease Genetic Network Study Rationale, Design, and Early Results

被引：129

作者：

Gelb, Bruce ^{[9
]}

Brueckner, Martina ^{[1
,10
]}

Chung, Wendy ^{[8
]}

Goldmuntz, Elizabeth ^{[3
,4
]}

Kaltman, Jonathan

Kaski, Juan Pablo

Kim, Richard ^{[13
]}

Kline, Jennie ^{[8
]}

Mercer-Rosa, Laura ^{[3
]}

Porter, George ^{[12
]}

Roberts, Amy ^{[6
]}

Rosenberg, Ellen

Seiden, Howard ^{[9
]}

Seidman, Christine ^{[3
,7
,16
]}

Sleeper, Lynn ^{[14
]}

Tennstedt, Sharon ^{[14
]}

Kaltman, Jonathan

Schramm, Charlene

Burns, Kristin

Pearson, Gail

Rosenberg, Ellen

Newburger, Jane ^{[6
]}

Breitbart, Roger ^{[6
,14
]}

Colan, Steven ^{[6
]}

Geva, Judith ^{[6
]}

Monafo, Angela ^{[6
]}

Roberts, Amy ^{[6
]}

Stryker, Janice ^{[6
,7
]}

Seidman, Christine ^{[3
,7
,16
]}

McDonough, Barbara ^{[3
]}

Seidman, Jonathan ^{[3
,15
]}

Goldmuntz, Elizabeth ^{[3
,4
]}

Edman, Sharon ^{[3
]}

Garbarini, Jennifer ^{[2
,3
]}

Hakonarson, Hakon ^{[3
]}

Mercer-Rosa, Laura ^{[3
]}

Mitchell, Laura ^{[3
]}

Tusi, Jessica ^{[3
]}

White, Peter ^{[3
]}

Woyciechowski, Stacy ^{[3
]}

Chung, Wendy ^{[8
]}

Warburton, Dorothy ^{[8
]}

Awad, Danielle ^{[8
]}

Celia, Katrina ^{[8
]}

Etwaru, Davina

Sond, Jaswinder Kaur ^{[8
]}

Kline, Jennie ^{[8
]}

Korsin, Rosalind ^{[8
]}

Lanz, Alyssa ^{[8
]}

Marquez, Emma ^{[8
]}

机构：

[1] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA

[2] UCL, Great Ormond St Hosp, London, England

[3] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[4] Univ Penn, Pennsylvania Perelman Sch Med, Philadelphia, PA 19104 USA

[5] New England Res Inst, Watertown, MA 02172 USA

[6] Childrens Hosp Boston, Boston, MA USA

[7] Brigham & Womens Hosp, Boston, MA 02115 USA

[8] Columbia Univ, New York, NY USA

[9] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[10] Yale Univ, New Haven, CT USA

[11] UCL, London, England

[12] Univ Rochester, Rochester, NY USA

[13] Childrens Hosp Los Angeles, Los Angeles, CA USA

[14] New England Res Inst, Data Coordinating Ctr, Watertown, MA 02172 USA

[15] Harvard Univ, Sch Med, Candidate Gene Evaluat & RNASeq, Boston, MA USA

[16] Harvard Univ, Sch Med, Boston, MA USA

[17] Univ Pittsburgh, Pittsburgh, PA 15260 USA

[18] NHLBI, Bethesda, MD 20892 USA

[19] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA

[20] Ohio State Univ, Coll Med, Columbus, OH 43210 USA

[21] Weill Cornell Med Coll, New York, NY USA

[22] Univ Wisconsin, Madison, WI 53706 USA

[23] Washington Univ, Sch Med, St Louis, MO 63130 USA

[24] Univ Iowa, Iowa City, IA 52242 USA

[25] Emory Univ, Atlanta, GA 30322 USA

[26] Cincinnati Childrens Hosp, Cincinnati, OH USA

来源：

CIRCULATION RESEARCH | 2013年 / 112卷 / 04期

关键词：

congenital cardiac defects; congenital heart disease; genome-wide analysis; genomic study; human genetics; COPY-NUMBER VARIATION; NKX2-5; MUTATIONS; NATIONAL HEART; DEFECTS; MALFORMATIONS; ASSOCIATION; TETRALOGY; VARIANTS; IDENTIFY; RISK;

D O I：

10.1161/CIRCRESAHA.111.300297

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome. (Circ Res. 2013; 127:698-706.)

引用

页码：698 / 706

页数：9

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