NOD2 and Cowden disease: Likely the most relevant genetic factors associated with a complicated course of CD are the three common mutations of the NOD2 protein, p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847), which have been associated with a complicated disease course of CD and in particular with a stricturing and penetrating disease behaviour.