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Unraveling the etiology of congenital heart defects – The role of maternal genetics and cardiovascular disease as a risk factor

Project description

Risk factors for congenital heart defects

Congenital heart defects (CHD) are structural anomalies that are present at birth and impact the function of a baby’s heart. CHD has been linked to genetic and environmental factors like maternal diabetes and obesity, but the underlying mechanisms remain poorly understood. Funded by the European Research Council, the FINNPEDHEART project is working under the hypothesis that maternal genetics and cardiovascular health contribute to the risk of giving birth to children with CHD. The project will retrospectively analyse data from Finish national health records to unveil important insights into the factors that influence early pregnancy cardiac development.

Objective

One in a hundred infants is born with a congenital heart defect (CHD). Both genetic and environmental risk factors, such as maternal diabetes and obesity, are known to cause CHD, however, little is known about the disease mechanisms behind these risks. CHD can occur as an element of a syndrome, in conjunction with other anomalies, or as an isolated defect. I propose that there is an etiologically distinct “environmental CHD” subgroup, where in addition to the child’s genes, maternal genetics and gene expression play a major role in disease development. Moreover, I propose that in these cases the genetic risk profile predisposes the woman for both having offspring with CHD and having early onset atherosclerotic disease.

My objective is to study how maternal genetics and maternal cardiovascular morbidity as an environmental risk contribute to the risk for having offspring with CHD. In addition, the multifactorial aetiology in terms of the presence of both risk factors, will be studied using a unique dataset available only in Finland. Three different substudies will be conducted: 1) Finnish national registers gathering health related information of all Finns from birth to death will be used to determine the presence of atherosclerosis and related traits, such as hypertension and coronary artery disease, in mothers who have offspring with CHD compared to those without (tot. N = 1 million). 2) Maternal genetic risk loci for having CHD in the offspring will be sought in the FinnGen study (tot. N = 0.5 million). 3) Maternal 1st trimester serum samples from pregnancies with and without CHD will be analysed to identify CHD associated biomarkers (tot. N = 3200).

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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2022-STG

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Host institution

HELSINGIN YLIOPISTO
Net EU contribution
€ 1 495 845,00
Address
FABIANINKATU 33
00014 Helsinki
Finland
Region
Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 495 845,00

Beneficiaries (1)