In addition to NOD2 polymorphisms, the risk of developing internal penetrating CD is significantly associated with the carriage of a variant allele of PRDM1 rs7746082, LOC441108, and IL23R. Specifically, the carriage of ATG16L1 and PRDM1 are independently associated with an earlier onset of internal penetrating disease in contrast to IL23R, which is associated with a later onset.51 Here, IL23R is linked to Cowden disease.