The first and most well-established gene with the greatest impact on IBD is caspase activating recruitment domain 15 (CARD15), also known as NOD2 (nucleotide-binding oligomerization domain-containing protein 2), which was discovered by Ogura et al. [48] within the IBD1 loci on chromosome 16q12 [38,40,49]. Here, NOD2 is linked to irritable bowel syndrome.