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

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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Alonso A,Domènech E,Julià A,Panés J,García-Sánchez V,Mateu PN,Gutiérrez A,Gomollón F,Mendoza JL,Garcia-Planella E,Barreiro-de Acosta M,Muñoz F,Vera M,Saro C,Esteve M,Andreu M,Chaparro M,Manyé J,Cabré E,López-Lasanta

doi

10.1053/j.gastro.2014.12.030

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

794-805

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(14)01582-0

journal_volume

148

pub_type

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