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. 2010 Nov 2;5(11):e13795.
doi: 10.1371/journal.pone.0013795.

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

Debby Laukens  1 , Michel Georges, Cécile Libioulle, Cynthia Sandor, Myriam Mni, Bert Vander Cruyssen, Harald Peeters, Dirk Elewaut, Martine De Vos
Affiliations

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

Debby Laukens et al. PLoS One. .

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Association of 36 SNPs known to influence CD risk with AS.
SNPs are ordered on the X-axis by increasing p-value. Y-axis: log10(1/p), corresponding to (i) nominal p-values (gray), (ii) Bonferroni corrected p-values (blue), (iii) expected distribution of p-values assuming that all SNPs are true null hypotheses (black), and (iv) the p-value of the distribution of individual p-values for the corresponding marker plus all the less significant ones (red). The horizontal line corresponds to a p-value of 0.05. The names of gene of interest in the vicinity of the associated SNPs as well as the number of genes in the confidence interval (defined according to [7]) are given for the five most interesting SNPs, exceeding the 0.05 significance threshold using the approach that extracts information from the p-value distribution.
See this image and copyright information in PMC

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