SNPwatch: Genetic Variant Linked to Cleft Lip

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.

John Henry “Doc” Holliday is rumored to have been born with a cleft lip and palate.

Beginning in the fourth week of gestation, the cells of a developing human fetus begin a complex program of rearrangements to form what will eventually become a child’s face.

In about one out of every 700 births this process goes awry. Genetic and environmental factors, acting alone or in concert, prevent the cells of the face from coming together properly, resulting in cleft lip and/or cleft palate. Though clefting can cause problems with feeding, ear infections and tooth development, surgery and other treatments can allow children to grow up to lead perfectly normal lives.

Although there are some rare genetic syndromes that cause cleft lip and/or palate, most cases of clefting are probably due to a combination of genetic factors that increase risk slightly and environmental triggers such as exposure to certain infections, some medications, alcohol and drug use, cigarette smoking, and certain vitamin deficiencies, especially during early pregnancy.

Fedik Rahimov and colleagues have now found the first common genetic variant, or SNP, strongly associated with cleft lip. Their results, published online Sunday in Nature Genetics, show that the common, non-inherited form of this condition is linked to a gene called IRF6 that was previously associated with a rare, dominantly inherited clefting disorder called Van der Woude syndrome.

Using 280 European families affected by cleft lip only, the researchers found that having one A at rs642961 increased the risk of this condition 1.91 times over the risk of those with two Gs at this SNP. That increase in risk rose to 2.29 times for people with two As.

Approximately 50% of people born with cleft lip also have a cleft palate. The link between rs642961 and cleft lip with cleft palate was not significant. Having cleft palate alone (no cleft lip) is rare, and there was no evidence that rs642961 was linked to this condition either.

(23andMe customers can check their data at a proxy SNP, rs861020, The version that increases risk of cleft is A for this SNP as well).

The authors note that the A version of rs642961 is least commonly found in Africans and most common in Native Americans, which mirrors the different levels of cleft lip and palate found in these populations. Because this research was conducted in Europeans, determining whether this SNP is associated with cleft lip in these populations will require further research.