Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants.

ABSTRACT: Congenital heart disease (CHD) is the most common birth defect and brings with it significant mortality and morbidity. The application of exome and genome sequencing has greatly improved the rate of genetic diagnosis for CHD but the cause in the majority of cases remains uncertain. It is clear that genetics, as well as environmental influences, play roles in the aetiology of CHD. Here we address both these aspects of causation with respect to the Notch signalling pathway. In our CHD cohort, variants in core Notch pathway genes account for 20% of those that cause disease, a rate that did not increase with the inclusion of genes of the broader Notch pathway and its regulators. This is reinforced by case-control burden analysis where variants in Notch pathway genes are enriched in CHD patient

SUBMITTER: Chapman G 

PROVIDER: S-EPMC7068028 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature