Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2016; 22(14): 3777-3784
Published online Apr 14, 2016. doi: 10.3748/wjg.v22.i14.3777
Multi-locus genetic risk score predicts risk for Crohn’s disease in Slovenian population
Katarina Zupančič, Kristijan Skok, Katja Repnik, Rinse K Weersma, Uroš Potočnik, Pavel Skok
Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia
Rinse K Weersma, Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 Groningen, The Netherlands
Pavel Skok, Department of Gastroenterology, University Medical Center, 2000 Maribor, Slovenia
Pavel Skok, Slovenia and Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia
Author contributions: Zupančič K and Skok K contributed equally to this work; Zupančič K, Skok K and Potočnik U designed the research; Zupančič K, Skok K and Repnik K performed the research; Zupančič K, Skok K and Skok P analyzed the data; Weersma RK contributed new data and analytic methods; Zupančič K, Skok K, Potočnik U and Skok P wrote the paper; Potočnik U, Repnik K and Skok P revised the article.
Institutional review board statement: The study was approved by the Slovenian National Committee for Medical Ethics (KME 80/10/ 07, 21p / 12/ 07 and 106/05/11).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at pavel.skok@guest.arnes.si.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pavel Skok, MD, PhD, Full Professor, Department of Gastroenterology, University Medical Center, Ljubljanska ulica 5, 2000 Maribor, Slovenia. pavel.skok@guest.arnes.si
Telephone: +386-23212878 Fax: +386-23212845
Received: January 16, 2016
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
Abstract

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.

Keywords: Inflammatory bowel disease; Crohn’s disease; Discriminatory accuracy; Genetic risk score; Single nucleotide polymorphisms

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.