Published online Apr 14, 2016. doi: 10.3748/wjg.v22.i14.3777
Peer-review started: January 18, 2016
First decision: February 18, 2016
Revised: March 1, 2016
Accepted: March 13, 2016
Article in press: March 14, 2016
Published online: April 14, 2016
Processing time: 72 Days and 19.7 Hours
AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population.
METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group.
RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.
CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.
Core tip: Genome wide association studies have provided a comprehensive catalogue of susceptibility inflammatory bowel disease (IBD) loci, which now present an important basis for genetic risk prediction. We aimed to develop an accurate Crohn’s disease (CD) risk prediction model for the Slovenian cohort. The most optimal 33 SNPs model showed good discriminatory ability, which may be useful for risk stratification in targeted population (gastrointestinal disturbances, positive family history). Individuals in the highest risk group have 27-fold higher odds for CD risk compared to individuals in the lowest risk group. To the best of our knowledge, this is the first population specific genetic prediction based on recently established IBD loci.