TY - JOUR
T1 - Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population
T2 - a case-control study
AU - Peter, Inga
AU - Mitchell, Adele A.
AU - Ozelius, Laurie
AU - Erazo, Monica
AU - Hu, Jianzhong
AU - Doheny, Dana
AU - Abreu, Maria T.
AU - Present, Daniel H.
AU - Ullman, Thomas
AU - Benkov, Keith
AU - Korelitz, Burton I.
AU - Mayer, Lloyd
AU - Desnick, Robert J.
N1 - Funding Information:
We would like to acknowledge the members of the New York Crohn’s Disease Genetics Group: Drs. James Aisenberg, Joel Bauer, Steven Itzkowitz, Barry Jaffin, Arthur Kornbluth, Simon Lichtiger, Peter Rubin, David Sachar, and Anthony Weiss. This work was funded by the New York Crohn’s Disease Foundation to BIK, LM, RJD.
PY - 2011/5/6
Y1 - 2011/5/6
N2 - 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.
AB - 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.
KW - Crohn's Disease Ashkenazi Jewish
KW - Genetic risk score
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U2 - 10.1186/1471-2350-12-63
DO - 10.1186/1471-2350-12-63
M3 - Article
C2 - 21548950
AN - SCOPUS:79955651296
SN - 1471-2350
VL - 12
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 63
ER -