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

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

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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.

Original languageEnglish
Article number63
JournalBMC Medical Genetics
Volume12
DOIs
StatePublished - May 6 2011

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Crohn Disease
Case-Control Studies
Population
Single Nucleotide Polymorphism
Alleles
Disease Susceptibility
Genes

Keywords

  • Crohn's Disease Ashkenazi Jewish
  • Genetic risk score

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population : a case-control study. / Peter, Inga; Mitchell, Adele A.; Ozelius, Laurie; Erazo, Monica; Hu, Jianzhong; Doheny, Dana; Abreu, Maria T; Present, Daniel H.; Ullman, Thomas; Benkov, Keith; Korelitz, Burton I.; Mayer, Lloyd; Desnick, Robert J.

In: BMC Medical Genetics, Vol. 12, 63, 06.05.2011.

Research output: Contribution to journalArticle

Peter, I, Mitchell, AA, Ozelius, L, Erazo, M, Hu, J, Doheny, D, Abreu, MT, Present, DH, Ullman, T, Benkov, K, Korelitz, BI, Mayer, L & Desnick, RJ 2011, 'Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study', BMC Medical Genetics, vol. 12, 63. https://doi.org/10.1186/1471-2350-12-63
Peter, Inga ; Mitchell, Adele A. ; Ozelius, Laurie ; Erazo, Monica ; Hu, Jianzhong ; Doheny, Dana ; Abreu, Maria T ; Present, Daniel H. ; Ullman, Thomas ; Benkov, Keith ; Korelitz, Burton I. ; Mayer, Lloyd ; Desnick, Robert J. / Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population : a case-control study. In: BMC Medical Genetics. 2011 ; Vol. 12.
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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.",
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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.

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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