The Congenital Heart Disease Genetic Network Study: Cohort description.

Thanh T Hoang,Bruce D Gelb,John E Deanfield,Laura E Mitchell,Sharon Edman,Wendy K Chung,Meghan Mac Neal,Adolfo Aleman,A J Agopian,Stacy Woyciechowski,Martina Brueckner,Richard P Lifton,Richard Kim,Alessandro Giardini,Amy E Roberts,George A Porter,Elizabeth Goldmuntz,Jennie K Kline,Robert W Dettman

doi:10.1371/journal.pone.0191319

Abstract

The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010–2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.

Highlights

Congenital heart defects (CHDs) occur in approximately 1% of births and are among the most common and serious birth defects [1, 2]
We provide a description of the phenotypes, characteristics, and selected parent-reported neurodevelopmental outcomes of the Pediatric Cardiac Genomics Consortium (PCGC) cohort, as a resource for the broader CHD research community
Between 2010 and 2014, the PCGC recruited over 9,000 families with a child affected by a CHD

Summary

Introduction

Congenital heart defects (CHDs) occur in approximately 1% of births and are among the most common and serious birth defects [1, 2]. CHD risk is thought to be influenced by both environmental and genetic factors, relatively few specific CHD risk factors have been identified and the extent to which the etiology of different CHDs differ or overlap is unknown. Large epidemiological studies, such as the National Birth Defect Prevention Study, have identified a few non-genetic risk factors for CHDs including maternal pre-gestational diabetes, obesity, and smoking [6,7,8,9,10]. The PCGC designed and implemented the Congenital Heart Disease GEnetic NEtwork Study (CHD GENES) to establish the resources required to undertake comprehensive studies of the genetics of CHDs

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Conclusion