NOD2 and Cowden disease: The first and most extensively replicated genetic findings in CD have been the association of 3 loss-of-function variants in NOD2 (nucleotide oligomerisation domain containing gene 2; p.R702W, p.G908R, and p.L1007insC), a gene important in mediating the early antimicrobial response.8–11 Cumulatively, these variants represent the strongest genetic risk factors identified for CD,12 and the many genome-wide association studies performed to date have yet to find a locus with a higher attributable risk.