The homozygous variant genotype of TLR1 743 T>C (rs4833095) (OR: 3.15, 95% confidence interval (CI): 1.59–6.26, p = 0.001) and TLR5 936 T>C (rs5744174) (OR: 1.54, 95% CI: 1.04–2.28, p = 0.03) and the combined homozygous and the heterozygous variant genotypes of IL12B G>C (rs6887695) (OR: 1.49, 95% CI: 1.13–1.96, p = 0.004) were associated with increased risk of CD. Here, TLR5 is linked to Cowden disease.