Our aim is to identify novel risk genes for congenital heart defects. Exome sequencing of Finnish congenital heart defect patients and their family members will be done to identify novel and extremely rare variants. Common risk variants for CHD are identified in FinnGen with genome wide association studies (GWAS). In addition, genetic variants associated with disease progress will be evaluated. We are focusing on three congenital heart defect subgroups in particular: left ventricular outflow tract obstruction defects, right ventricular outflow tract obstruction defects, and transposition of the great arteries.
Our aim is to study cellular and molecular mechanisms behind congenital heart defects in patient-derived human induced pluripotent stem cells (hiPSCs). The hiPSCs are differentiated into cardiomyocytes (CMs) and endothelial cells (ECs) and examined in disease models including monoculture, coculture, and under flow. In addition, new potentially pathogenic genes/variants identified in the exome sequencing study will be evaluated in using these cell models.
The objective of the FINNPEDHEART project is to study how maternal genetics and maternal cardiovascular morbidity contribute to the risk for having offspring with CHD using maternal first trimester serum samples, Finnish nationwide register data, and genomic data from the FInnGen project. The study results will provide important information on how the combination of maternal genetic and environmental risk factors contribute to cardiac developmental defects during early pregnancy and offer new insights for future research on the cellular and molecular mechanisms of cardiac development.