Congenital Heart Disease GEnetic NEtwork Study (CHD GENES) (CHD GENES)

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Heart Defects

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Eileen King, PhD; Email: B2BProgram@cchmc.org

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N3JH
    • Completed
    • University College London
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
      • Contact: Shreya Anand; Phone Number: 323-361-1432; Email: sanand@chla.usc.edu
      • Principal Investigator: Jon Cleveland, MD
    • Palo Alto, California, United States, 94304
      • Completed
      • Stanford University
    • San Francisco, California, United States, 94158
      • Completed
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Nancy Cross; Phone Number: 203-737-6835; Email: nancy.cross@yale.edu
      • Principal Investigator: Martina Brueckner, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Children's Hospital Boston
      • Contact: Judith Geva, MSW; Phone Number: 617-355-4979; Email: judith.geva@cardio.chboston.org
      • Principal Investigator: Amy Roberts, MD
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham & Women's Hospital
      • Contact: Barbara McDonough, RN; Phone Number: 617-432-1006; Email: mcdonough@genetics.med.harvard.edu
      • Principal Investigator: Christine Seidman, MD
  • New York
    • New Hyde Park, New York, United States, 11040
      • Completed
      • Cohen Children's Medical Center New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Emily Griffin; Phone Number: 212-342-3101; Email: eg2871@cumc.columbia.edu
      • Principal Investigator: Wendy K Chung, MD, PHD
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai School of Medicine
      • Contact: Priyal Agrawal; Phone Number: 212-241-4321; Email: priyal.agrawal@mssm.edu
      • Principal Investigator: Bruce Gelb, MD
    • Rochester, New York, United States, 14642
      • Completed
      • University of Rochester
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Completed
      • Children's Hospital Philadelphia
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • University of Utah
      • Contact: Kristin Konery; Phone Number: 801-213-7618; Email: Kristin.Konery@hsc.utah.edu
      • Principal Investigator: Martin Tristani-Firouzi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

• Signed consent form

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Amy Roberts, MD, Childrens Hospital Boston; Principal Investigator: Christine Seidman, MD, Harvard Medical School, Boston MA; Principal Investigator: Bruce Gelb, MD, Mt Sinai School of Medicine, New York NY; Principal Investigator: Martina Brueckner, MD, Yale University; Principal Investigator: Martin Tristani-Firouzi, MD, University of Utah; Principal Investigator: Wendy Chung, MD, PhD, Columbia University Medical Center, New York NY; Principal Investigator: Jon Cleveland, Children's Los Angeles

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Click here for more information about the entire Bench to Bassinet program.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2010
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 3, 2010
• First Submitted That Met QC Criteria: September 3, 2010
• First Posted (Estimated): September 8, 2010

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 701; 5U01HL098188-03 (U.S. NIH Grant/Contract); U01HL098188 (U.S. NIH Grant/Contract); U01HL098147 (U.S. NIH Grant/Contract); U01HL098163 (U.S. NIH Grant/Contract); U01HL098153 (U.S. NIH Grant/Contract); U01HL098123 (U.S. NIH Grant/Contract); U01HL098162 (U.S. NIH Grant/Contract)