RNF186 and Crohn disease: In addition to PTVs in the genes identified here, we also investigated PTVs in genes with previously identified protective effects such as: CARD9, RNF186, and IL23R shown to confer protection against Crohn’s disease and/or ulcerative colitis1,2; ANGPTL4, PCSK9, LPA, and APOC3 shown to confer protection against coronary heart disease4,13–17; and SCN9A where homozygous PTV carriers show an inability to experience pain59 (Supplementary Table 1).