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Am J Gastroenterol DOI:10.1038/ajg.2013.464

Differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis: analysis of a North American cohort.

Publication TypeJournal Article
Year of Publication2014
AuthorsAnanthakrishnan, AN, Huang, H, Nguyen, DD, Sauk, J, Yajnik, V, Xavier, RJ
JournalAm J Gastroenterol
Volume109
Issue3
Pages395-400
Date Published2014 Mar
ISSN1572-0241
KeywordsAdolescent, Adult, Cohort Studies, Colitis, Ulcerative, Crohn Disease, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Nod2 Signaling Adaptor Protein, North America, Phenotype, Prospective Studies, Risk Assessment, Risk Factors, Young Adult
Abstract

OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases with a progressive relapsing remitting course. There is considerable heterogeneity in disease course and accurate prediction of natural history has been challenging. The phenotypic implication of increasing genetic predisposition to CD or UC is unknown.

METHODS: The data source for our study was a prospective cohort of CD and UC patients recruited from a tertiary referral center. All patients underwent genotyping on the Illumina Immunochip. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for each of the 163 inflammatory bowel disease (IBD) risk loci was calculated and phenotypic associations examined across GRS quartiles.

RESULTS: Our study cohort included 1,105 patients (697 CD, 408 UC). Increasing genetic burden was associated with earlier age of diagnosis of CD (Ptrend=0.008). Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile. Increasing genetic burden was also associated with ileal involvement in CD (Ptrend

CONCLUSIONS: Increasing genetic burden is associated with early age of diagnosis in CD, but not UC. The expanded panel of IBD risk loci explains only a fraction of variance of disease phenotype, suggesting limited clinical utility of genetics in predicting natural history.

URLhttp://dx.doi.org/10.1038/ajg.2013.464
DOI10.1038/ajg.2013.464
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24419484?dopt=Abstract

Alternate JournalAm. J. Gastroenterol.
PubMed ID24419484
PubMed Central IDPMC4225079
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
U01 DK062432 / DK / NIDDK NIH HHS / United States
R01 DK064869 / DK / NIDDK NIH HHS / United States
K23 DK097142 / DK / NIDDK NIH HHS / United States
DK097142 / DK / NIDDK NIH HHS / United States