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Gastroenterology. 2015 Apr;148(4):794-805. doi: 10.1053/j.gastro.2014.12.030. Epub 2014 Dec 31.

Identification of risk loci for Crohn's disease phenotypes using a genome-wide association study.

Author information

1
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.
2
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.
3
Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
4
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.
5
Digestive System Service, Universidad de Córdoba/Instituto Maimónides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía, Córdoba, Spain.
6
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Digestive Medicine Service, Hospital la Fe, Valencia, Spain.
7
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital General de Alicante, Alicante, Spain.
8
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Digestive System Service, Hospital Clínico Universitario, Zaragoza, Spain.
9
Gastroenterology Service, Hospital Clínico San Carlos, Madrid, Spain.
10
Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
11
Gastroenterology Service, Hospital Clínico Universitario, Santiago de Compostela, Spain.
12
Gastroenterology Service, Complejo Hospitalario de León, León, Spain.
13
Gastroenterology Service, Hospital Universitario Puerta de Hierro, Madrid, Spain.
14
Internal Medicine Service, Hospital de Cabueñes, Gijón, Spain.
15
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Gastroenterology Service, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
16
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.
17
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.
18
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.
19
Life Sciences, Barcelona Supercomputing Center, National Institute of Bioinformatics, Barcelona, Spain; Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
20
National DNA Bank Carlos III, University of Salamanca, Salamanca, Spain.
21
Nacional Genotyping Centre, Universitat Pompeu Fabra, Barcelona, Spain.
22
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
23
Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain. Electronic address: sara.marsal@vhir.org.

Abstract

BACKGROUND & AIMS:

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.

KEYWORDS:

Clinical Outcome; Genetic Risk; IBD; SNP

PMID:
25557950
DOI:
10.1053/j.gastro.2014.12.030
[Indexed for MEDLINE]

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