Tu1904 Towards Individualised Risk Prediction for Crohn's Disease

Abstract

Introduction Although the RR of developing Crohn9s disease (CD) is increased in first degree relatives (FDR) of probands by 13–27-fold, (1) it is difficult to apply this on an individual basis. Recently, risk models for complex disease using information from genome-wide association and epidemiological studies have been built. Potentially, such models could identify FDR at highest risk of CD, for screening and early intervention. Aim To generate a risk model for CD, and ultimately determine if such a model can predict presymptomatic or future development of CD. Methods CD patients were contacted to identify asymptomatic FDR aged 18–55 who wished to participate in research into risk prediction and presymptomatic diagnosis of CD. (Recruitment target: 500 FDR) DNA was extracted from saliva. Genetic analysis used the Immunochip (Illumina), and genotypes were determined for disease susceptibility loci established by CD genome-wide meta-analysis. (2) A multiplicative risk model was generated using risk prediction software (REGENT) (3) based on genotype and smoking status, and CD RR determined for each FDR. Results The first 100 FDR have been recruited. Demographics: 53% siblings, 36% offspring, 11% parents. Mean age 37, females 66%, smokers 25%, ex-smokers 33%. NOD2 genotype counts were not significantly different to their frequencies in the control population, but were significantly different to cases (13% heterozygous, 0% homozygous, p=0.64 for controls vs FDR, p=0.001 for cases vs FDR). CD RR ranged from 0.04 to 10.07 (median 0.96) and was significantly higher than that in the general population: 19% of FDR had a RR >2, compared to an expected proportion of 11% (p=0.02). Comparison of highest and lowest RR quartiles in FDR showed good separation of RR between the groups. More FDRs in the highest RR quartile had >2 CD-affected relatives compared with FDRs in the lowest RR quartile, but this was not significant (5 vs 1, p=0.19). Conclusion Increased RR of CD is confirmed in FDR compared to the general population. Risk stratification is possible, but follow-up is required to determine if such risk scores can be used to predict presymptomatic CD or future development of CD. Additionally, risk awareness may encourage smokers to quit. Once recruitment to the study is completed, FDR in the highest and lowest risk quartiles will proceed to further tests including faecal and serum biomarkers, and capsule endoscopy. All those recruited will undergo follow-up for 10 years. Competing interests None declared.