Our observations support these studies but highlight a subset of IBD cases molecularly defined by recessive inheritance of NOD2 alleles that exhibit markedly increased risk for CD with significantly earlier age of onset (mean age of onset among recessive NOD2 carriers in the DiscovEHR IBD cohort: 43.4y; mean age of onset in the DiscovEHR IBD cohort: 51.5y; P-value: 4.0X10–4 by unpaired t test). Here, NOD2 is linked to Cowden disease.