title: 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.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Julià
authors.affiliation: Gastroenterology and Hepatology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD).
authors.forename: Eugeni
authors.initials: E
authors.lastname: Domènech
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Service, Hospital Universitario de la Princesa and IP, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.affiliation: Digestive System Service, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Valle
authors.initials: V
authors.lastname: García-Sánchez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Digestive System Service, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomollón
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Department, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
authors.affiliation: Gastroenterology and Hepatology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD).
authors.forename: Míriam
authors.initials: M
authors.lastname: Mañosa
authors.affiliation: Gastroenterology Service, Hospital Clínico Universitario, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Barreiro-De Acosta
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Service, Hospital General de Alicante, Alicante, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.affiliation: Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Garcia-Planella
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Digestive Medicine, University and Polytechnic La Fe Hospital, Valencia, Spain.
authors.forename: Mariam
authors.initials: M
authors.lastname: Aguas
authors.affiliation: Gastroenterology Service, Complejo Hospitalario de León, León, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Muñoz
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Service, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
authors.affiliation: Gastroenterology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mendoza
authors.affiliation: Gastroenterology Service, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Vera
authors.affiliation: Department of Gastroenterology, IMIM. (Hospital del Mar Medical Research Institute), Pompeu Fabra University, Barcelona, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Márquez
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: Raül
authors.initials: R
authors.lastname: Tortosa
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López-Lasanta
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: Arnald
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Life Sciences, Barcelona Supercomputing Centre, National Institute of Bioinformatics, Barcelona, Spain Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Josep L
authors.initials: JL
authors.lastname: Gelpí
authors.affiliation: Banco Nacional de ADN Carlos III, University of Salamanca, Salamanca, Spain.
authors.forename: Andres C
authors.initials: AC
authors.lastname: García-Montero
authors.affiliation: Nacional Genotyping Centre (CeGen), Universitat Pompeu Fabra, Barcelona, Spain and.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Gastroenterology Service, Hospital Universitario de la Princesa and IP, Madrid, Spain javier.p.gisbert@gmail.com.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Marsal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D021901:DNA, Intergenic; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: C000599332:CALHM6 protein, human; D021901:DNA, Intergenic; D008562:Membrane Glycoproteins