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Enrichment for rare pathogenic and highly damaging variants in congenital heart disease patients

Year: 2020
Type: article
Study design: Observational Study
Abstract: Congenital heart disease (CHD), defined as any structural abnormality of the heart or great vessels, is a leading cause of morbidity and mortality in infants and young children. Even as survival rates for the most severe forms of CHD improve, patients still face a lifetime of monitoring, diagnostic procedures, and possible additional surgeries to address these defects or related issues. Compounding matters is recent evidence suggesting CHD patients may have an increased lifetime risk of developing cancer either due to some of the same genetic mutations that caused the CHD or as a result of other extrinsic factors such as repeated exposure to radiation during diagnostic or interventional procedures. The genetic etiology of CHD is quite complex with both sporadic and familial forms as well as monogenic forms with simple Mendelian inheritance and multigenic forms with complex inheritance patterns. This study investigated whether CHD patients have an increased burden of rare pathogenic or highly damaging variants in genes known to be associated with congenital heart defects or cancer. My results indicate pathogenic and highly damaging variants in some genes with a known association with CHD, but not in genes associated with cancer play a role in the etiology of heart development. Furthermore, these results appear to be consistent with a complex multigenic model of CHD. Finally, they suggest that variants in genes related to response to oxygen levels may serve as a prognostic indicator. However, this study has several limitations, the most notable being a nonrandom sample population and a lack of control for population substructure. In spite of these limitations, I feel that this research provides a good foundation on which to base future more in-depth analyses with more statistical power. This research is of public health importance as it can help shed light on the genetic etiology of CHD and provide insight into which patients may be at greater risk for later complications which in turn could lead to improved diagnostics, treatment, and preventative measures.
Language: English
Open Access status: green
OpenAlex ID: W3119595976
FWCI:
Cites: 330
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Related to: 10