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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2011

Open Access 01-12-2011 | Research article

Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study

Authors: Inga Peter, Adele A Mitchell, Laurie Ozelius, Monica Erazo, Jianzhong Hu, Dana Doheny, Maria T Abreu, Daniel H Present, Thomas Ullman, Keith Benkov, Burton I Korelitz, Lloyd Mayer, Robert J Desnick, the New York Crohn's Disease Working Group

Published in: BMC Medical Genetics | Issue 1/2011

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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.
Appendix
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Metadata
Title
Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study
Authors
Inga Peter
Adele A Mitchell
Laurie Ozelius
Monica Erazo
Jianzhong Hu
Dana Doheny
Maria T Abreu
Daniel H Present
Thomas Ullman
Keith Benkov
Burton I Korelitz
Lloyd Mayer
Robert J Desnick
the New York Crohn's Disease Working Group
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-12-63

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