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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Antigens, CD / genetics*
  • Case-Control Studies
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Chloride Channels / genetics*
  • Chromosomes, Human, Pair 2 / genetics*
  • Crohn Disease / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Guanylate Kinases
  • Humans
  • Lectins, C-Type / genetics*
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics*
  • White People / genetics


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • CLCA2 protein, human
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Chloride Channels
  • DEC-205 receptor
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • Guanylate Kinases
  • MAGI1 protein, human