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

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 childs 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.