title: Identification of risk loci for Crohn's disease phenotypes using a genome-wide association study.
abstract: OBJECTIVE
  Crohn's disease is a highly heterogeneous inflammatory bowel disease comprising multiple clinical phenotypes. Genome-wide association studies (GWASs) have associated a large number of loci with disease risk but have not associated any specific genetic variants with clinical phenotypes. We performed a GWAS of clinical phenotypes in Crohn's disease.
  
  
  METHODS
  We genotyped 576,818 single-nucleotide polymorphisms in a well-characterized cohort of 1090 Crohn's disease patients of European ancestry. We assessed their association with 17 phenotypes of Crohn's disease (based on disease location, disease behavior, disease course, age at onset, and extraintestinal manifestations). A total of 57 markers with strong associations to Crohn's disease phenotypes (P < 2 × 10(-4)) were subsequently analyzed in an independent replication cohort of 1296 patients of European ancestry.
  
  
  RESULTS
  We replicated the association of 4 loci with different Crohn's disease phenotypes. Variants in MAGI1, CLCA2, 2q24.1, and LY75 loci were associated with a complicated stricturing disease course (Pcombined = 2.01 × 10(-8)), disease location (Pcombined = 1.3 × 10(-6)), mild disease course (Pcombined = 5.94 × 10(-7)), and erythema nodosum (Pcombined = 2.27 × 10(-6)), respectively.
  
  
  CONCLUSIONS
  In a GWAS, we associated 4 loci with clinical phenotypes of Crohn's disease. These findings indicate a genetic basis for the clinical heterogeneity observed for this inflammatory bowel disease.
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain; Department of Enginyeria de Sistemes, Automática i Informàtica Industrial, Polytechnic University of Catalonia, Barcelona, Spain.
authors.forename: Arnald
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Gastroenterology and Hepatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. Electronic address: edomenech.germanstrias@gencat.cat.
authors.forename: Eugeni
authors.initials: E
authors.lastname: Domènech
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Julià
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
authors.affiliation: Digestive System Service, Universidad de Córdoba/Instituto Maimónides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía, 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, Barcelona, Spain; Digestive Medicine Service, Hospital la Fe, Valencia, Spain.
authors.forename: Pilar Nos
authors.initials: PN
authors.lastname: Mateu
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital General de Alicante, Alicante, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Digestive System Service, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomollón
authors.affiliation: Gastroenterology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mendoza
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: Gastroenterology Service, Hospital Clínico Universitario, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Barreiro-de Acosta
authors.affiliation: Gastroenterology Service, Complejo Hospitalario de León, León, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Muñoz
authors.affiliation: Gastroenterology Service, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Vera
authors.affiliation: Internal Medicine Service, Hospital de Cabueñes, Gijón, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Saro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
authors.affiliation: Department of Gastroenterology, Institut Hospital del Mar d'Investigacions Mèdiques, Institute of Research Hospital del Mar, Parc de Salut Mar, Pompeu Fabra University, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital Universitario de la Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Chaparro
authors.affiliation: Gastroenterology and Hepatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Manyé
authors.affiliation: Gastroenterology and Hepatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Cabré
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López-Lasanta
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Raül
authors.initials: R
authors.lastname: Tortosa
authors.affiliation: Life Sciences, Barcelona Supercomputing Center, National Institute of Bioinformatics, Barcelona, Spain; Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Gelpí
authors.affiliation: National DNA Bank Carlos III, University of Salamanca, Salamanca, Spain.
authors.forename: Andrés C
authors.initials: AC
authors.lastname: García-Montero
authors.affiliation: Nacional Genotyping Centre, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain. Electronic address: sara.marsal@vhir.org.
authors.forename: Sara
authors.initials: S
authors.lastname: Marsal
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital Universitario de la Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D051528:Guanylate Kinases; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C120066:CLCA2 protein, human; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D018118:Chloride Channels; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D051528:Guanylate Kinases; C113338:MAGI1 protein, human
keywords: Clinical Outcome; Genetic Risk; IBD; SNP