A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300

• Published in: Gut Vol. 62; no. 10; pp. 1440 - 1445
• Main Authors: Julià, Antonio, Domènech, Eugeni, Ricart, Elena, Tortosa, Raül, García-Sánchez, Valle, Gisbert, Javier P, Nos Mateu, Pilar, Gutiérrez, Ana, Gomollón, Fernando, Mendoza, Juan Luís, Garcia-Planella, Esther, Barreiro-de Acosta, Manuel, Muñoz, Fernando, Vera, Maribel, Saro, Cristina, Esteve, Maria, Andreu, Montserrat, Alonso, Arnald, López-Lasanta, María, Codó, Laia, Gelpí, Josep Lluís, García-Montero, Andres C, Bertranpetit, Jaume, Absher, Devin, Panés, Julián, Marsal, Sara
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.10.2013; BMJ Publishing Group LTD
• Subjects: Adult; Autoimmune diseases; Carrier Proteins - genetics; Case-Control Studies; Chromosomes; Chromosomes, Human, Pair 22 - genetics; Consortia; Crohn Disease - epidemiology; Crohn Disease - genetics; Crohn's Disease; Crohns disease; DNA, Intergenic - genetics; E1A-Associated p300 Protein - genetics; Family medical history; Female; Gene banks; Genealogy; Genetic Loci - genetics; Genetic Polymorphisms; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genotype; Humans; Inflammatory bowel disease; Inflammatory diseases; Male; Middle Aged; Polymorphism, Single Nucleotide; Population; Power; Spain - epidemiology; Studies; Spain; Genetics; Crohn's Disease; Genetic Polymorphisms
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2012-302865

Objective Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn's disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci. Design We genotyped 620 901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls. Results We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk. Conclusions In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.