|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Ananthakrishnan, AN, Huang, H, Nguyen, DD, Sauk, J, Yajnik, V, Xavier, RJ|
|Journal||Am J Gastroenterol|
|Date Published||2014 Mar|
|Keywords||Adolescent, 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|
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.
|Alternate Journal||Am. J. Gastroenterol.|
|PubMed Central ID||PMC4225079|
|Grant List||P30 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