title: Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.
abstract: BACKGROUND
  Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population.
  
  
  METHODS
  We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value.
  
  
  RESULTS
  Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16).
  
  
  CONCLUSIONS
  CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029 USA. inga.peter@mssm.edu
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Adele A
authors.initials: AA
authors.lastname: Mitchell
authors.forename: Laurie
authors.initials: L
authors.lastname: Ozelius
authors.forename: Monica
authors.initials: M
authors.lastname: Erazo
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Hu
authors.forename: Dana
authors.initials: D
authors.lastname: Doheny
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Present
authors.forename: Thomas
authors.initials: T
authors.lastname: Ullman
authors.forename: Keith
authors.initials: K
authors.lastname: Benkov
authors.forename: Burton I
authors.initials: BI
authors.lastname: Korelitz
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D007585:Jews / Q000235:genetics*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012372:ROC Curve; D012044:Regression Analysis