Independent replication of an association of CNVR7113.6 with Crohn's disease in caucasians
Version of Record online: 10 MAY 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 2, pages 305–311, February 2012
How to Cite
Roberts, R. L., Diaz-Gallo, L.-M., Barclay, M. L., Gómez-García, M., Cardeña, C., Merriman, T. R., Gearry, R. B. and Martin, J. (2012), Independent replication of an association of CNVR7113.6 with Crohn's disease in caucasians. Inflamm Bowel Dis, 18: 305–311. doi: 10.1002/ibd.21752
- Issue online: 10 JAN 2012
- Version of Record online: 10 MAY 2011
- Manuscript Accepted: 31 MAR 2011
- Manuscript Received: 6 MAR 2011
- Health Research Council (HRC) of New Zealand and the Junta de Andalucia. Grant Number: CTS-180
- Sir Charles Hercus Health Research Fellowship (HRC)
- Ayudas Predoctorales de Formación en Investigación en Salud. Grant Number: PFIS – FI09/00544
- copy number polymorphism;
- chromosomal rearrangement;
- inflammatory bowel disease;
- ulcerative colitis;
- 17q21 locus
A recent genome-wide association study (GWAS) of copy number variants (CNVs) in Crohn's disease (CD) confirmed association of three CNVs. The GWAS also provided evidence that a fourth CNV, CNVR7113.6, on chromosome 17 may alter susceptibility to CD (P = 0.0018). The aim of our study was to confirm the CNVR7113.6 association by genotyping two independent inflammatory bowel disease (IBD) cohorts and by conducting a subsequent meta-analysis.
In all, 1369 New Zealand Caucasians (489 CD patients, 463 ulcerative colitis [UC] patients, and 417 controls) and 2737 Spanish Caucasians (711 CD patients, 549 UC patients, and 1477 controls) were genotyped for a single nucleotide polymorphism (SNP), rs413778, in high linkage disequilibrium (r2 = >0.99) with CNVR7113.6. Chi-square analysis was conducted to test for association of rs413778 with overall CD, UC, IBD, and with disease phenotype. New Zealand and Spanish genotypes were then combined with imputed rs413778 genotypes from the Wellcome Trust Case Control Consortium (WTCCC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) CD datasets to conduct a meta-analysis.
The minor allele of rs413778 conferred protection against CD in the Spanish cohort (CD: P = 0.004, odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.71–0.94). A similar, albeit nonsignificant protective effect was observed in New Zealand CD patients (P = 0.098, OR = 0.83, 95% CI: 0.66–1.04). No association with UC or disease phenotypes was detected in either cohort. Meta-analysis found significant cumulative evidence for a protective effect of rs413778 in Caucasian CD (P = 1.19E-05, OR = 0.86, 95% CI: 0.80–0.92).
This study provides the first independent replication of the association of CNVR7113.6 with CD. (Inflamm Bowel Dis 2011;)