Insights into the genetic architecture underlying complex, critical congenital heart disease

Gillian M Blue; Eddie K K Ip; Michael Troup; Russell C Dale; Gary F Sholler; Richard P Harvey; Sally L Dunwoodie; Eleni Giannoulatou; David S Winlaw

doi:10.1016/j.ahj.2022.09.006

Insights into the genetic architecture underlying complex, critical congenital heart disease

Am Heart J. 2022 Dec:254:166-171. doi: 10.1016/j.ahj.2022.09.006. Epub 2022 Sep 15.

Authors

Gillian M Blue¹, Eddie K K Ip², Michael Troup², Russell C Dale³, Gary F Sholler¹, Richard P Harvey⁴, Sally L Dunwoodie⁵, Eleni Giannoulatou⁵, David S Winlaw⁶

Affiliations

¹ Heart Centre for Children, The Children's Hospital at Westmead, Sydney, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia.
² Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia.
³ Sydney Medical School, The University of Sydney, Sydney, Australia.
⁴ Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia; School of Biotechnology and Biomolecular Science, UNSW Sydney, Sydney, Australia.
⁵ Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, Australia.
⁶ Heart Centre for Children, The Children's Hospital at Westmead, Sydney, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia; Cincinnati Children's Hospital Medical Center, Heart Institute, Cardiothoracic Surgery, Cincinnati, OH. Electronic address: david.winlaw@cchmc.org.

PMID: 36115390
DOI: 10.1016/j.ahj.2022.09.006

Abstract

Congenital heart disease (CHD) has a multifactorial aetiology, raising the possibility of an underlying genetic burden, predisposing to disease but also variable expression, including variation in disease severity, and incomplete penetrance. Using whole genome sequencing (WGS), the findings of this study, indicate that complex, critical CHD is distinct from other types of disease due to increased genetic burden in common variation, specifically among established CHD genes. Additionally, these findings highlight associations with regulatory genes and environmental "stressors" in the final presentation of disease.

Publication types

Letter

MeSH terms

Heart Defects, Congenital* / genetics
Humans