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Evidence for significant overlap between common risk variants for Crohn's disease and ankylosing spondylitis

Debby Laukens UGent, Michel Georges, Cécile Libioulle, Cynthia Sandor, Myriam Mni, BERT VANDER CRUYSSEN UGent, Harald Peeters UGent, Dirk Elewaut UGent and MARTINE DE VOS UGent (2010) PLOS ONE. 5(11).
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CELLS, JOINT, ASTHMA, GENOME-WIDE ASSOCIATION, INFLAMMATORY-BOWEL-DISEASE, SUSCEPTIBILITY, GENE, CONTRIBUTE, EXPRESSION, IL23R
journal title
PLOS ONE
PLoS One
volume
5
issue
11
article_number
e13795
pages
4 pages
Web of Science type
Article
Web of Science id
000283779700009
JCR category
BIOLOGY
JCR impact factor
4.411 (2010)
JCR rank
12/84 (2010)
JCR quartile
1 (2010)
ISSN
1932-6203
DOI
10.1371/journal.pone.0013795
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
1094867
handle
http://hdl.handle.net/1854/LU-1094867
date created
2011-01-06 10:07:42
date last changed
2011-01-07 16:16:06
@article{1094867,
  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.},
  articleno    = {e13795},
  author       = {Laukens, Debby and Georges, Michel and Libioulle, C{\'e}cile and Sandor, Cynthia and Mni, Myriam and VANDER CRUYSSEN, BERT and Peeters, Harald and Elewaut, Dirk and DE VOS, MARTINE},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {CELLS,JOINT,ASTHMA,GENOME-WIDE ASSOCIATION,INFLAMMATORY-BOWEL-DISEASE,SUSCEPTIBILITY,GENE,CONTRIBUTE,EXPRESSION,IL23R},
  language     = {eng},
  number       = {11},
  pages        = {4},
  title        = {Evidence for significant overlap between common risk variants for Crohn's disease and ankylosing spondylitis},
  url          = {http://dx.doi.org/10.1371/journal.pone.0013795},
  volume       = {5},
  year         = {2010},
}

Chicago
Laukens, Debby, Michel Georges, Cécile Libioulle, Cynthia Sandor, Myriam Mni, BERT VANDER CRUYSSEN, Harald Peeters, Dirk Elewaut, and MARTINE DE VOS. 2010. “Evidence for Significant Overlap Between Common Risk Variants for Crohn’s Disease and Ankylosing Spondylitis.” Plos One 5 (11).
APA
Laukens, D., Georges, M., Libioulle, C., Sandor, C., Mni, M., VANDER CRUYSSEN, B., Peeters, H., et al. (2010). Evidence for significant overlap between common risk variants for Crohn’s disease and ankylosing spondylitis. PLOS ONE, 5(11).
Vancouver
1.
Laukens D, Georges M, Libioulle C, Sandor C, Mni M, VANDER CRUYSSEN B, et al. Evidence for significant overlap between common risk variants for Crohn’s disease and ankylosing spondylitis. PLOS ONE. 2010;5(11).
MLA
Laukens, Debby, Michel Georges, Cécile Libioulle, et al. “Evidence for Significant Overlap Between Common Risk Variants for Crohn’s Disease and Ankylosing Spondylitis.” PLOS ONE 5.11 (2010): n. pag. Print.