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Evidence for Significant Overlap between Common Risk Variants for Crohn's Disease and Ankylosing Spondylitis

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
5
Issue
11
Identifiers
DOI: 10.1371/journal.pone.0013795
Keywords
  • Research Article
  • Genetics And Genomics/Gene Expression
  • Genetics And Genomics/Genetics Of Disease
  • Gastroenterology And Hepatology/Inflammatory Bowel Disease
  • Rheumatology/Autoimmunity
  • Autoimmune
  • And Inflammatory Diseases
Disciplines
  • Biology

Abstract

Background A multicenter genome-wide association scan for Crohn's Disease (CD) has recently reported 40 CD susceptibility loci, including 29 novel ones (19 significant and 10 putative). To gain insight into the genetic overlap between CD and ankylosing spondylitis (AS), these markers were tested for association in AS patients. Principal Findings Two previously established associations, namely with the MHC and IL23R loci, were confirmed. In addition, rs2872507, which maps to a locus associated with asthma and influences the expression of the ORMDL3 gene in lymphoblastoid cells, showed a significant association with AS (p = 0.03). In gut biopsies of AS and CD patients, ORMDL3 expression was not significantly different from controls and no correlation was found with the rs2872507 genotype (Spearman's rho: −0.067). The distribution of p-values for the remaining 36 SNPs was significantly skewed towards low p-values unless the top 5 ranked SNPs (ORMDL3, NKX2–3, PTPN2, ICOSLG and MST1) were excluded from the analysis. Conclusions Association analysis using risk variants for CD led to the identification of a new risk variant associated with AS (ORMDL3), underscoring a role for ER stress in AS. In addition, two known and five potentially relevant associations were detected, contributing to common susceptibility of CD and AS.

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