Genetics of Congenital Heart Disease

April 1, 2026 updated by: Vidu Garg, Nationwide Children's Hospital

Genetic Testing of Individuals and Families With Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect but the cause for the majority of cardiac birth defects remains unknown. Numerous epidemiologic studies have demonstrated evidence that genetic factors likely play a contributory, if not causative, role in CHD. While numerous genes have been identified by us and other investigators using traditional genetic approaches, these genes account for a minority of the non-syndromic CHDs. Therefore, we are now utilizing whole genome sequencing (WGS), with the addition of more traditional genetic techniques such as chromosomal microarray or traditional linkage analysis, to identify genetic causes of familial and isolated CHD. With WGS we are able to sequence all of the genetic material of an individual and apply different data analysis techniques based on whether we are analyzing a multiplex family or a cohort of trios (mother, father and child with CHD) with a specific isolated CHD. Therefore, WGS is a robust method for identification of novel genetic causes of CHD which will have important diagnostic and therapeutic consequences for these children.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Congenital heart disease (CHD) is the most common type of birth defect, but the etiology of CHD remains largely unknown. Genetic causes have been discovered for both syndromic and non-syndromic CHD utilizing several genetic approaches (Yasuhara and Garg, 2021). The majority of these genetic causes have found by studying large families with autosomal dominant congenital heart disease and my laboratory has successfully used this methodology in the past (Garg, 2003; Garg 2005; Pan, 2009; Bennett, 2022). Although these positional cloning approaches are very powerful, they are limited by rare nature of multi-generation pedigrees and are limited to milder forms of CHD that have allowed for the generation of large kindreds.

The other method that has traditionally been utilized to identify genetic causes of CHD is the screening of large populations of children with sporadic (non-familial) cases of CHD for genetic abnormalities (nucleotide sequence variations in candidate genes for CHD or for chromosomal copy number changes that involve CHD-candidate genes). This work has been tedious as a large number of candidate genes have been implicated as potentially responsible for CHD in humans (Choudhury and Garg, 2022). Although this approach has been successful (Schluterman, 2007; Maitra, 2010; Chang, 2013; Bonachea, 2014), it is also limited to the candidate gene lists.

Whole exome sequencing (WES) is a next-generation sequencing technology that allows for the sequencing of all of the expressed genes. Our group, in addition to several others (LaHaye, 2016; Gordon, 2022), has been utilizing WES technology for CHD gene discovery. Our group has progressed to utilizing whole genome sequencing (WGS), a next-generation sequencing technology that allows for the sequencing of all genetic material (including genomic regions that are not sequenced in WES), in our analysis for CHD gene discovery. Therefore, these sequencing methods can be applied to multiplex families and cohorts of sporadic cases to identify genetic causes of CHD in an unbiased manner. Genomic sequencing is dependent on the technical and bioinformatics prowess of the personnel running the sequencing and the controlling the data pipeline. The Institute of Genomic Medicine at Nationwide Children's Hospital (NCH) is both technically skilled and have developed their own powerful data pipeline (Kelly, 2015). WGS is a powerful genetic tool that can be used in isolation or in conjunction with other types of genetic analysis to increase the yield of these investigations.

Study Type

Observational

Enrollment (Estimated)

5000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Recruiting
        • Nationwide Children's Hospital
        • Principal Investigator:
          • Vidu Garg, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

cardiology clinic sample, community sample

Description

Inclusion Criteria:

  • Subjects must have a diagnosis of Congenital Heart Disease or be related to individuals with Congenital Heart Disease.

Exclusion Criteria:

  • Healthy individuals unrelated to those with Congenital Heart Disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Study Subjects
Individuals with Congenital Heart Disease and family members with or without Congenital Heart Disease. A blood sample collection will be required for all study participants.
Other: Blood Sample Collection
Blood sample collection for direct sequencing, microarray, single nucleotide polymorphism, whole-genome array comparative genomic hybridization DNA analyses, and/or whole exome or genome sequencing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of novel genetic contributors to congenital heart defects
Time Frame: up to 3 years, from date of genetic analysis to completion of genetic data analysis or identification of novel genetic contributors, whichever comes first
Novel genetic abnormalities that are found to be associated with congenital heart defects in humans
up to 3 years, from date of genetic analysis to completion of genetic data analysis or identification of novel genetic contributors, whichever comes first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nationwide Children's Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Vidu Garg, MD, Nationwide Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

August 30, 2010

First Submitted That Met QC Criteria

August 30, 2010

First Posted (Estimated)

August 31, 2010

Study Record Updates

Last Update Posted (Actual)

April 7, 2026

Last Update Submitted That Met QC Criteria

April 1, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB09-00339
  • R01HL109758 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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