Project: PeRsOnalized Genomics For CongEniTal HEart Disease

Acronym PROCEED (Reference Number: ERAPERMED2018-293)
Duration 01/03/2019 - 28/02/2022
Project Topic Congenital heart disease (CHD) is the leading cause of newborn deaths. Its genetic cause remains elusive in 80% cases. We will use whole genome sequencing to explore the human genome to find gene defects that cause CHD – tetralogy of Fallot (TOF) and transposition of the great arteries (TGA), and determine how these gene defects predict severity of heart disease and outcomes. 684 patients have already been sequenced which has revealed novel causes of CHD not previously reported e.g. defects in new genes and defects outside of genes in regions that control gene expression. The research team has developed an automated bioinformatics pipeline that allows interpreting gene defects found in whole genome data in a matter of hours. The research team from Canada (Ontario) and Europe (Netherlands, Germany) will access samples from their population biorepositories to sequence another 1000 children and adults with CHD. This will help confirm whether the findings in the original cohort can be replicated in a larger patient cohort. These gene defects will then be validated by studying if they change gene expression in patient tissue or in cellular assays. This will help validate the automated interpretation pipeline for CHD so that it can be shared with the broader scientific community for genomic interpretation. The tool will also be licensed to a genetic testing lab for incorporation into their CHD diagnostics pipeline for clinical translation. The ability to individualize risk prediction based on genotype will help personalize reproductive counselling and help personalize management of CHD families. Families can opt for pre-emptive strategies to prevent CHD in future pregnancy through pre-implantation genetic testing for complex CHD. Genetic based prediction of outcomes can inform timing and type of fetal and postnatal interventions. A better understanding of the genomic architecture of CHD may eventually enable gene correction strategies in eligible cases in the future.
Network ERA PerMed
Call 1st Joint Transnational Call for Proposals (2018)

Project partner

Number Name Role Country
1 The Hospital for Sick Children Coordinator Canada
2 University of Amsterdam Partner Netherlands
3 St. Antonius Hospital Partner Netherlands
4 Schleswig-Holstein University Hospital Partner Germany
5 DNAStack Partner Canada