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Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French Canadians, the most prominent founder population in North America.Using well-characterized phenotype data in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-IBD Genetics Consortium repository on patients with IBD, we compared phenotypic characteristics of 202 French Canadians with those of 1,287 other Caucasian patients. These included diagnosis, anatomical location, disease behavior, extraintestinal manifestations, surgical history, and family history of IBD.French-Canadian patients with Crohn's disease (CD) were less likely to have stricturing disease (11 vs. 21%,P=0.005; odds ratio (OR): 0.45, 95% confidence interval (95% CI): 0.24-0.85). Using a stringent definition of ethnicity (three out of four grandparents being French Canadians, as opposed to self-report,n=148), French Canadians had a tendency toward developing fistulizing CD (37 vs. 28%,P=0.07), and there was an increased prevalence of sacroiliitis among those with IBD (4 vs. 2%,P=0.045). Among French Canadians, the numbers of current smokers in CD (40 vs. 25%,P=0.006) and former smokers in ulcerative colitis (UC) (35 vs. 20%,P=0.03) were significantly higher. The prevalence of one of the three main variants of nucleotide-binding oligomerization domain containing 2 (NOD2) single-nucleotide polymorphisms (SNPs)-among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French Canadians (75 vs. 0%,P= 0.006).French Canadians show an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to the management of IBD in this population.