CD63 and Cowden disease: Our observations are in line with previous analyses and meta-analyses of CD cohorts where individuals carrying any one of the main three CD associated risk alleles (p.R702W, p.G908R, or p.L1007fs) have 2–fourfold increased risk for developing CD63, whereas carriers of two or more of the same NOD2 variants have a 15–40 fold increased risk for developing CD33,64,65, exhibiting disease of the terminal ileum34, and earlier diagnosis (by an average of 3 years)33.