Variation in the gene DGKK is a strong risk factor for hypospadias, according to a study published online this week in Nature Genetics.
Hypospadias is a common birth defect in boys in which the opening of the urethra is displaced along the ventral side of the penis. To identify genetic risk factors for hypospadias, Loes van der Zanden, Barbara Franke and colleagues performed a genome-wide association study of individuals from The Netherlands with or without this malformation, with follow-up testing in two independent sample collections from The Netherlands and Sweden. The researchers identified common genetic variation in DGKK that was consistently associated with two- to three-fold higher risk of hypospadias.
According to the findings, DGKK is expressed in the foreskin region and its expression is lower in boys carrying the risk-associated variant.