Congenital heart defects (CHDs) continue to be the leading cause of death among all infants with birth defects. It is reported that approximately 10% of cardiac congenital anomalies have a genetic basis. An equal percentage, or ~10%, is due to environmental factors. For ~60% the etiology is unknown and considered to have a multifactorial basis, eg, environmental agents having a role against a specific genetic background, as with obese and diabetic mothers who are at increased risk for giving birth to a child with heart defects. Most studies, however, address CHDs by manipulating only single specific genes and analyzing effects. Except for rare diseases in which single gene mutations may be involved, most tend to be multifactorial.