Clinical trial NCT01196182: Congenital Heart Disease GEnetic NEtwork Study (CHD GENES)
Official title: Congenital Heart Disease GEnetic NEtwork Study (CHD GENES)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Heart Defects
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2010-09-08
Enrollment: 10000
Sex: ALL
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: While all patients with pediatric cardiovascular disease and adults with congenital heart disease are of interest, the study will initially focus on four CHD anatomic classifications:

* Atrial septal defects
* Conotruncal abnormalities
* Left-sided obstructive lesions
* Heterotaxy

Whenever possible, the study will recruit "trios" of participants--children, mothers and fathers-- as well as extended family members when appropriate and feasible.

Brief summary: Congenital heart defects (CHD) are the most common major human birth malformation, affecting \~8 per 1,000 live births. CHD are associated with significant morbidity and mortality, and are second only to infectious diseases in contributing to the infant mortality rate. Current understanding of the etiology of pediatric cardiovascular disorders is limited.

The Congenital Heart Disease GEnetic NEtwork Study (CHD GENES) is a multi-center, prospective observational cohort study. Participants will be recruited from the Pediatric Cardiac Genomics Consortium's (PCGC) centers of the NHLBI-sponsored Bench to Bassinet (B2B) Program. Biological specimens will be obtained for genetic analyses, and phenotype data will be collected by interview and from medical records. State-of-the-art genomic technologies will be used to identify common genetic causes of CHD and genetic modifiers of clinical outcome.

To accomplish this, the PCGC will develop and maintain a biorepository of specimens (DNA) and genetic data, along with detailed, phenotypic and clinical outcomes data in order to investigate relationships between genetic factors and phenotypic and clinical outcomes in congenital heart disease.


Eligibility criteria: Inclusion Criteria:

• Signed consent form

Exclusion Criteria:

* Isolated patent foramen ovale
* Isolated prematurity-associated patent ductus arteriosus

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center New York
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: Childrens Hospital Boston
name: Amy Roberts, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard Medical School, Boston MA
name: Christine Seidman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mt Sinai School of Medicine, New York NY
name: Bruce Gelb, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Martina Brueckner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Martin Tristani-Firouzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University Medical Center, New York NY
name: Wendy Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Los Angeles
name: Jon Cleveland
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morton SU, Pereira AC, Quiat D, Richter F, Kitaygorodsky A, Hagen J, Bernstein D, Brueckner M, Goldmuntz E, Kim RW, Lifton RP, Porter GA Jr, Tristani-Firouzi M, Chung WK, Roberts A, Gelb BD, Shen Y, Newburger JW, Seidman JG, Seidman CE. Genome-Wide De Novo Variants in Congenital Heart Disease Are Not Associated With Maternal Diabetes or Obesity. Circ Genom Precis Med. 2022 Apr;15(2):e003500. doi: 10.1161/CIRCGEN.121.003500. Epub 2022 Feb 7.
citation: Oluwafemi OO, Musfee FI, Mitchell LE, Goldmuntz E, Xie HM, Hakonarson H, Morrow BE, Guo T, Taylor DM, McDonald-McGinn DM, Emanuel BS, Agopian AJ. Genome-Wide Association Studies of Conotruncal Heart Defects with Normally Related Great Vessels in the United States. Genes (Basel). 2021 Jul 1;12(7):1030. doi: 10.3390/genes12071030.
citation: Lahrouchi N, Postma AV, Salazar CM, De Laughter DM, Tjong F, Piherova L, Bowling FZ, Zimmerman D, Lodder EM, Ta-Shma A, Perles Z, Beekman L, Ilgun A, Gunst Q, Hababa M, Skoric-Milosavljevic D, Stranecky V, Tomek V, de Knijff P, de Leeuw R, Robinson JY, Burn SC, Mustafa H, Ambrose M, Moss T, Jacober J, Niyazov DM, Wolf B, Kim KH, Cherny S, Rousounides A, Aristidou-Kallika A, Tanteles G, Ange-Line B, Denomme-Pichon AS, Francannet C, Ortiz D, Haak MC, Ten Harkel AD, Manten GT, Dutman AC, Bouman K, Magliozzi M, Radio FC, Santen GW, Herkert JC, Brown HA, Elpeleg O, van den Hoff MJ, Mulder B, Airola MV, Kmoch S, Barnett JV, Clur SA, Frohman MA, Bezzina CR. Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy. J Clin Invest. 2021 Mar 1;131(5):e142148. doi: 10.1172/JCI142148.
citation: Sharma A, Wasson LK, Willcox JA, Morton SU, Gorham JM, DeLaughter DM, Neyazi M, Schmid M, Agarwal R, Jang MY, Toepfer CN, Ward T, Kim Y, Pereira AC, DePalma SR, Tai A, Kim S, Conner D, Bernstein D, Gelb BD, Chung WK, Goldmuntz E, Porter G, Tristani-Firouzi M, Srivastava D, Seidman JG, Seidman CE; Pediatric Cardiac Genomics Consortium. GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm. Elife. 2020 Oct 15;9:e53278. doi: 10.7554/eLife.53278.
citation: Boskovski MT, Homsy J, Nathan M, Sleeper LA, Morton S, Manheimer KB, Tai A, Gorham J, Lewis M, Swartz M, Alfieris GM, Bacha EA, Karimi M, Meyer D, Nguyen K, Bernstein D, Romano-Adesman A, Porter GA Jr, Goldmuntz E, Chung WK, Srivastava D, Kaltman JR, Tristani-Firouzi M, Lifton R, Roberts AE, Gaynor JW, Gelb BD, Kim R, Seidman JG, Brueckner M, Mayer JE Jr, Newburger JW, Seidman CE. De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease. Circ Genom Precis Med. 2020 Aug;13(4):e002836. doi: 10.1161/CIRCGEN.119.002836. Epub 2020 Jun 30.