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

TitleIdentification of risk loci for Crohn’s disease phenotypes using a genome-wide association study
Publication TypeJournal Article
Year of Publication2015
AuthorsAlonso, Arnald, Domènech Eugeni, Julià Antonio, Panés Julián, García-Sánchez Valle, Mateu Pilar Nos, Gutiérrez Ana, Gomollón Fernando, Mendoza Juan L., Garcia-Planella Esther, de Acosta Manuel Barreiro-, Muñoz Fernando, Vera Maribel, Saro Cristina, Esteve Maria, Andreu Montserrat, Chaparro María, Manyé Josep, Cabré Eduard, López-Lasanta María, Tortosa Raül, Gelpí Josep-Lluis, García-Montero Andres C., Bertranpetit Jaume, Absher Devin, Myers Richard M., Marsal Sara, and Gisbert Javier P.
Date Published2015 Apr
KeywordsAdult, Antigens, C-Type, Case-Control Studies, CD, Cell Adhesion Molecules, Cell Surface, Chloride Channels, Chromosomes, Crohn Disease, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Human, Humans, Lectins, Male, Middle Aged, Neuronal, Pair 2, Phenotype, Polymorphism, Receptors, Single Nucleotide

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.