SNP8, SNP12, and SNP13 have differential effects on CD risk, with SNP13 having the strongest genetic effect. These NOD2 variants are also significant risk factors for CD phenotype, in particular ileal location.

Seventy-five years after the initial characterization of Crohn's disease (CD), much remains obscure about its etiology. The authors sought to evaluate the incidence trends of the last 25 years worldwide, and the existence of potential correlations with genetic, environmental, and socioeconomic factors that could be etiologically implicated in the pathogenesis of CD. Relevant medical literature for individual countries on the incidence of CD, on the incidence of associated genetic mutations, and on the incidence of suggested etiologic infectious agents such as Mycobacterium avium paratuberculosis were retrieved from published medical literature, reports from relevant international congresses, and through official reports from national health authorities. Increasing trends have been observed almost worldwide, with a broad north-south gradient still prevailing in Europe. Distinct regions of New Zealand, Canada, Scotland, France, the Netherlands, and Scandinavia represent the highest incidence areas. Industrialized status and affluence are the common denominators between endemic areas, but are too broad as terms to strongly indicate any particular etiological role. The increasing trends observed in Asia still account for a low prevalence of the disease and may represent increased detection and diagnostic ability of local health systems. Genetic associations are variably reproduced worldwide, in a manner inconsistent with a strong etiologic relationship. Data on paratuberculosis incidence are scarce, and the existing ones are ambivalent regarding an even indirect correlation between CD and an infectious trigger.