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


RESULTS
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.
Department of Gastroenterology, Ghent University, Ghent, Belgium.
Debby
D
Laukens
Michel
M
Georges
Cécile
C
Libioulle
Cynthia
C
Sandor
Myriam
M
Mni
Bert
B
Vander Cruyssen
Harald
H
Peeters
Dirk
D
Elewaut
Martine
M
De Vos
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D055815:Young Adult
D008565:Membrane Proteins; C464399:ORMDL3 protein, human