This is evidenced by a significantly increased risk among first-degree relatives and the identification of over 200 genetic risk loci through genome-wide association studies (GWAS) [32]. Siblings of affected individuals have 35 times more risk of developing the disease than the general population [33]. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is identified as the most important genetic factor influencing CD [34]. NOD2 is critical in bacterial sensing, and ATG16L1 is involved in autophagy, and together they are strongly linked to CD susceptibility [35]. Here, NOD2 is linked to Cowden disease.