SNPwatch: Common Genetic Factors Associated with “Blue Babies”

Image by Mariana Ruiz LadyofHats [Public domain], via Wikimedia Commons

New research suggests that a once-fatal congenital heart defect — sometimes called “blue baby syndrome” — is influenced by genetic factors that are broadly found in the general population. Different heart malformations lead to poor oxygenation of the blood and a bluish discoloration of the skin, but the most common culprit (affecting three in 10,000 births) is a condition called tetralogy of Fallot (fah-LO), or TOF. Before the first heart surgery was pioneered for this condition in the mid 1940’s, about 80 percent of affected children died before the age of ten.

Like most heart malformations that arise in the womb, it’s not possible to point to a single causative factor for TOF. A number of non-genetic factors increase risk — alcoholism and diabetes in the mother as well as poor nutrition and certain infections during pregnancy. But there are also hints that TOF is more common in some families, raising the possibility that genetics also plays a role.

The new study led by Dr. Heather Cordell from the Institute of Genetic Medicine in Newcastle provides insight into the genetic underpinnings of TOF. Dr. Cordell and colleagues carried out the first genome-wide association study (GWAS) on this condition in around 1,600 people of European ancestry and found two genetic markers (or SNPs) associated with TOF. Their findings were published in the journal Human Molecular Genetics.

The first marker () is located in a region of chromosome 12 (12q24) that has previously been associated with numerous complex conditions including coronary artery disease and autoimmune disease. The second marker () is located in a gene called GPC5 that encodes a protein called glypican 5. Previous studies have linked deletions near this gene with heart malformations including TOF.  A few other markers were also suggestively linked to TOF and it’s possible that future, larger studies might solidify their involvement.

This is the first study to suggest that common genetic factors in the developing fetus play a role in TOF. Roughly 30 percent of people have at least one risky version of the SNPs discussed here, but each variant only increases risk slightly. Babies who are GG at are about 1.3 times more likely to be born with TOF while babies who are AC or AA at are about 1.3-1.7 times more likely to have TOF. Combine these genetic factors with environmental cues and the scale might tip towards TOF.

February is American Heart Month. Check out other posts on heart health:
Genetics and a Healthy Heart
A New Health Report To Take To Heart

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who received their health information prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will only have access to ancestry information as well as access to their uninterpreted raw data. These new customers may receive health reports in the future dependent on FDA marketing authorization.

  • Afiq Zamri

    Is the environmental factors (non-genetical) such as diet of a mother, or the genetic factors influence more for a baby to have TOF?

    • BethannH

      More research is needed to really be able to answer your question. Many different factors seem to be involved (alcoholism in the mother, diabetes, being an older mother, poor nutrition during pregnancy, rubella or other viral illnesses during pregnancy, etc) but genetics also seems to play a role. Babies with TOF are more likely to have chromosomal disorders like Down syndrome and as this blog post shows, relatively common genetic factors may also increase risk for TOF. Read more here:

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