For example, NOD2, a significant risk factor for ileal CD, is highly expressed in PCs, as shown by genome-wide association studies (GWASs).104,350,351 Economou and colleagues performed a meta-analysis and found that the CD risk is significantly increased in individuals with two mutated Nod2 alleles (17.1-fold) and Nod2 heterozygotes (2.4-fold).352 The mRNA expression of DEF5A (the gene encoding HD5) in PCs is significantly reduced in patients with a Nod2 mutation compared to patients with CD expressing wild-type Nod2 (ref. 62). This evidence concerns the gene DEFA5 and Cowden disease.