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News

Genetic burden influences disease phenotypes in IBD

This month's American Journal of Gastroenterology reports differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis.

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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 Crohn's disease or ulcerative colitis is unknown.

Dr Ashwin Ananthakrishnan and colleagues from Massachussetts, USA performed a prospective cohort study of Crohn's disease and ulcerative colitis 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.

The team evaluated 1,105 patients.

The researchers found that an increasing genetic burden was associated with earlier age of diagnosis of Crohn's disease.

Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile.

The team noted that increasing genetic burden was also associated with ileal involvement in Crohn's disease.

The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers.

The research team observed that ulcerative colitis patients with an involved first-degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in ulcerative colitis.

Dr Ananthakrishnan's team concludes, "Increasing genetic burden is associated with early age of diagnosis in Crohn's disease, but not ulcerative colitis."

"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."

Am J Gastroenterol 2014; 109: 395–400
17 March 2014

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