For exceptions such as an HLA SNP associated with rheumatoid arthritis, Crohn disease, and enteric fever (Dunstan et al., 2014, Freudenberg et al., 2011, Yamazaki et al., 2013), our observation of association with systemic TNF-α levels suggests a different mechanistic association instead of the classical hypothesis of modifying disease risk via antigen-specific effects. This evidence concerns the gene TNF and Crohn disease.