In CD, it has long been known that low frequency coding variants in NOD2 make a substantial contribution to disease risk [7–9], and more recent high-throughput sequencing strategies have discovered several independent IBD associated rare variants in NOD2 and other genes from GWAS loci including IL23R, CARD9, IL18RAP, CUL2, C1orf106, PTPN22, RNF186 and MUC19 [10–12]. This evidence concerns the gene NOD2 and inflammatory bowel disease.