Established genetic risk factors do not distinguish early and later onset Crohn's disease.

ABSTRACT

BACKGROUND: Early-onset disease is frequently examined in genetic studies because it is presumed to contain a more severe subset of patients under a higher influence of genetic effects. In light of the dramatic success of Crohn's disease (CD) gene discovery efforts, we aimed to characterize the contribution of established common risk variants to pediatric CD. METHODS: Using 35 confirmed CD risk alleles, we genotyped 384 parent-child trios (mean age of onset 11.7 years) along with 321 healthy controls. We performed association tests on the independent pediatric cohort and compared results to those previously published.1 We also computed a weighted CD genetic risk score for each affected person. Six variants not previously validated in children (at 5q33, 1q24, 7p12, 12q12, 8q24, and 1q32) were significantly associated with pediatric CD (P < 0.03). RESULTS: We detected no significant association between risk score and age at onset through age 30. This analysis illustrates that the genetic effect of established CD risk variants is similar in early and later onset CD. CONCLUSIONS: These results motivate joint analyses of genome-wide association data in early and late onset cohorts and suggest that, rather than established risk variants, independent variants or environmental exposures should be sought as modulators of age of onset.