A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.

Abstract

The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

• Authors: Antonio Julià, Eugeni Domènech, María Chaparro, Valle García-Sánchez, Fernando Gomollón, Julián Panés, Míriam Mañosa, Manuel Barreiro-De Acosta, Ana Gutiérrez, Esther Garcia-Planella, Mariam Aguas, Fernando Muñoz, Maria Esteve, Juan L Mendoza, Maribel Vera, Lucía Márquez, Raül Tortosa, María López-Lasanta, Arnald Alonso, Josep L Gelpí, Andres C García-Montero, Jaume Bertranpetit, Devin Absher, Richard M Myers, Javier P Gisbert, Sara Marsal
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 25 Pg. 6927-34 (Dec 20 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 25082827 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• CALHM6 protein, human
• DNA, Intergenic
• Membrane Glycoproteins

Topics

• Adult
• Case-Control Studies
• Chromosomes, Human, Pair 6
• Colitis, Ulcerative (genetics, pathology)
• DNA, Intergenic
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Male
• Membrane Glycoproteins (genetics)
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide