title: Multi-locus genetic risk score predicts risk for Crohn's disease in Slovenian population.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Zupančič
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Kristijan
authors.initials: K
authors.lastname: Skok
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Repnik
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Uroš
authors.initials: U
authors.lastname: Potočnik
authors.affiliation: Katarina Zupančič, Kristijan Skok, Katja Repnik, Uroš Potočnik, Center for Human Genetics and Pharmacogenomics, Medical Faculty of Maribor, University of Maribor, 2000 Maribor, Slovenia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Skok
mesh_terms: D019540:Area Under Curve; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D017524:Slovenia
chemical_list: D005819:Genetic Markers
keywords: Crohn’s disease; Discriminatory accuracy; Genetic risk score; Inflammatory bowel disease; Single nucleotide polymorphisms