Further, while we observe a low effect size for single allele carriers, based on our allelic effect size calculations for each of the 3 main CD risk alleles in our DiscovEHR cohort (Table 3, Fig. 3), we hypothesize that homozygous and compound heterozygous NOD2 individuals included in large IBD GWAS cohorts have likely contributed to a large proportion of the relative risk calculations for IBD, specifically for CD, under additive models, and that homozygous effect sizes have been largely underappreciated or underreported. Here, NOD2 is linked to Cowden disease.