The Genetic Basis of Congenital Heart Disease in Africa

The International Genetic Basis of Congenital Heart Disease Study

Recent advances in genomic techniques are making possible a new wave of genetic discovery in congenital heart disease (CHD). Existing data suggests that CHD occur in Sub-Saharan Africa at frequencies similar to the rest of the world. In this application, we propose to utilize the unique advantages of Sub-Saharan Africa - a combination of the most genetically diverse populations in the world and of diminished environmental background effects (i.e. low prevalence of smoking, alcohol abuse, obesity in comparison to western countries) - to better understand the genetic basis for congenital heart disease. We will couple next generation genomic techniques with more traditional gene discovery methods to investigate CHD in two African countries: Uganda and Nigeria. The inclusion of syndromic and non-syndromic CHD observed in these populations as well as careful phenotyping (including echocardiography) will greatly enhance our potential to provide insight into the genetic architecture of CHD in African populations. To accomplish this, we plan to enroll families, in whom members have congenital heart malformations consistent with an error of early human development in our research protocol. Patients will be enrolled at the Uganda Heart Institute in Kampala, Uganda, and at the Department of Pediatrics, College of Medicine, University of Lagos, Nigeria, with the potential to include other African sites. High throughput genomic studies will be done at the NIH....

Study Overview

• Status: Completed
• Conditions: Heart Disease; Congenital Heart Disease

Detailed Description

Recent advances in genomic techniques are making possible a new wave of genetic discovery in congenital heart disease (CHD). Existing data suggests that CHD occur in Sub-Saharan Africa at frequencies similar to the rest of the world. In this application, we propose to utilize the unique advantages of Sub-Saharan Africa - a combination of the most genetically diverse populations in the world and of diminished environmental background effects (i.e. low prevalence of smoking, alcohol abuse, obesity in comparison to western countries) - to better understand the genetic basis for congenital heart disease. We will couple next generation genomic techniques with more traditional gene discovery methods to investigate CHD in two African countries: Uganda and Nigeria. The inclusion of syndromic and non-syndromic CHD observed in these populations as well as careful phenotyping (including echocardiography) will greatly enhance our potential to provide insight into the genetic architecture of CHD in African populations. To accomplish this, we plan to enroll families, in whom members have congenital heart malformations consistent with an error of early human development in our research protocol. Patients will be enrolled at the Uganda Heart Institute in Kampala, Uganda, and at the Department of Pediatrics, College of Medicine, University of Lagos, Nigeria, with the potential to include other African sites. High throughput genomic studies will be done at the NIH.

• Study Type: Observational
• Enrollment (Actual): 1231

Contacts and Locations

Study Locations

• Nigeria
  • Lagos, Nigeria
    • College of Medicine, University of Lagos
• Thailand
  • Chiangmai, Thailand
    • Chiang Mai University
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Childrens National Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study will include affected individuals and their affected/or unaffected family members. Family members will include parents and siblings. The goal will to be obtaining a minimum of a trio (affected and both parents) to increase probability of finding gene mutations. Clinical criteria for inclusion is defined as presence of a congenital cardiac malformation related to errors in early human development. The diagnosis of congenital heart disease (presence of a congenital cardiac malformation thought to be related to errors in early human development) will be made by a cardiologist on our team based on echocardiogram, physical examination, medical history, and review of medical record.

Description

• INCLUSION CRITERIA:

The study will include affected individuals and their affected/or unaffected family members. Family members will include parents and siblings. The goal will to be obtaining a minimum of a trio (affected and both parents) to increase probability of finding gene mutations. Clinical criteria for inclusion is defined as presence of a congenital cardiac malformation related to errors in early human development. The diagnosis of congenital heart disease (presence of a congenital cardiac malformation thought to be related to errors in early human development) will be made by a cardiologist on our team based on echocardiogram (performed by C.S., A.B. or E.E.), physical examination, medical history, and review of medical record.

EXCLUSION CRITERIA:

Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Congenital Heart Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic Diagnosis	The primary outcome is a genetic diagnosis for congenital heart disease. There are no treatments.	One patient visit only

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)
• Collaborators: University of Lagos, Nigeria; Uganda Heart Institute
• Investigators: Principal Investigator: Adebowale A Adeyemo, M.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

General Publications

• Ekure EN, Adeyemo A, Liu H, Sokunbi O, Kalu N, Martinez AF, Owosela B, Tekendo-Ngongang C, Addissie YA, Olusegun-Joseph A, Ikebudu D, Berger SI, Muenke M, Han Z, Kruszka P. Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa. Circ Genom Precis Med. 2021 Feb;14(1):e003108. doi: 10.1161/CIRCGEN.120.003108. Epub 2021 Jan 15.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2013
• Primary Completion (Actual): June 22, 2021
• Study Completion: June 22, 2021

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: September 24, 2013
• First Posted (Estimated): September 27, 2013

Study Record Updates

• Last Update Posted (Estimated): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: January 9, 2024

More Information

Terms related to this study

• Keywords: Natural History; Congenital Heart Disease; Birth Defects; Genomics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: 999913207; 13-HG-N207

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No