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

ABSTRACT: 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.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).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.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.

SUBMITTER: Essers JB

PROVIDER: S-EPMC2768775 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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

Essers Jonah B JB Lee Jessica J JJ Kugathasan Subra S Stevens Christine R CR Grand Richard J RJ Daly Mark J MJ

Inflammatory bowel diseases 20091001 10

<h4>Background</h4>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.<h4>Methods</h4>Using 35 confirmed CD risk alleles, we genotyped 384 parent-child trios (mean age of onset 11.7 years) along with 32 ...[more]

PMID: 19322901

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Project description:BackgroundPediatric chronic pain (i.e., pain lasting ≥ 3 months) is prevalent, disabling, and costly. It spikes in adolescence, interrupts psychosocial development and functioning, and often co-occurs with mental health problems. Chronic pain often begins spontaneously without prior injuries and/or other disorders. Prospective longitudinal cohort studies following children from early childhood, prior to chronic pain onset, are needed to examine contributing factors, such as early pain experiences and mental health. Using data from a longitudinal community pregnancy cohort (All Our Families; AOF), the present study examined the associations between early developmental risk factors, including early childhood pain experiences and mental health symptoms, and the onset of pediatric chronic pain at ages 8 and 11 years.MethodsAvailable longitudinal AOF data from child age 4 months, as well as 1, 2, 3, 5, 8, and 11 years, were used. Mothers reported their child's pain experiences (e.g., hospitalizations, vaccinations, gut problems) at each timepoint from 4 months to 8 years, child chronic pain at age 8, and child mental health symptoms at ages 5 and 8 years. Children reported their chronic pain frequency and interference at age 11. Adaptive least absolute shrinkage and selection operator (LASSO) regressions were used to select predictor variables. Complete case analyses were complemented by multiple imputation using chained equation (MICE) models.ResultsGut problems, emergency room visits, frequent pain complaints, and headaches at age 5 or earlier, as well as female sex, were associated with increased risk of maternal reported child chronic pain at age 8. Maternal reported chronic pain at age 8 was associated with higher levels of child-reported pain frequency and pain interferences at age 11. Boys self-reported lower levels of pain interference at age 11.ConclusionsSome, but not all, painful experiences (e.g., gut problems, ER visits, pain complaints) in early life contribute to pediatric chronic pain onset and should be considered for screening and early intervention.

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

Publications

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

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