Ashwin N Ananthakrishnan, Hailiang Huang, Deanna D Nguyen, Jenny Sauk, Vijay Yajnik, and Ramnik J Xavier. 2014. “Differential effect of genetic burden on disease phenotypes in Crohn’s disease and ulcerative colitis: analysis of a North American cohort.” Am J Gastroenterol, 109, 3, Pp. 395-400. Abstract
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 <0.0001). The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers. UC patients with an involved first-degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in UC.
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.