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Roberts, R.L. et al.

Rebecca L. Roberts, Lina-Marcela Diaz-Gallo, Murray L. Barclay, María Gómez-García, Carlos Cardeña, Tony R. Merriman, Richard B. Gearry, Javier Martin,

Independent replication of an association of CNVR7113.6 with Crohn's disease in caucasians.

BACKGROUND: 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. METHODS: 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 (r(2) = >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. RESULTS: 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). CONCLUSIONS: This study provides the first independent replication of the association of CNVR7113.6 with CD. (Inflamm Bowel Dis 2011;).[1]

References

Independent replication of an association of CNVR7113.6 with Crohn's disease in caucasians. Roberts, R.L., Diaz-Gallo, L.M., Barclay, M.L., Gómez-García, M., Cardeña, C., Merriman, T.R., Gearry, R.B., Martin, J. Inflamm. Bowel Dis. (2012) [Pubmed]

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