CD patients with ATG16L1T300A genotype who are smokers had the most severe Paneth cell defects.27 Smoking-induced Paneth cell defects in ATG16L1T300A mice were rescued by Peroxisome proliferator-activated receptor gamma (Ppar-γ) agonist rosiglitazone treatment.68 Thereby, in vitro and animal model studies can complement our knowledge of interactions between gene-environment regarding the IBD pathogenesis and lead us much closer to the potential therapeutic solutions. Here, PPARG is linked to Cowden disease.