highly significantP < 1 × 10 −16
Next-generation sequencing in pooled samples from patients with Crohn's disease and controls identified additional independent risk variants in two of the known risk genes ( NOD2 and IL23R ), a highly significant association with a protective splice variant in CARD9 ( P < 1 × 10 −16 , odds ratio ∼0.29), and additional associations with coding variants in several genes ( IL18RAP , CUL2 , C1orf106 , PTPN22 and MUC19 ) ( Rivas et al. , 2011 ).