Association between genetic variants in myosin IXB and Crohn's disease.
BACKGROUND
Genetic variation in myosin IXB (MYO9B) was found to be associated with ulcerative colitis (UC) in a recent collaborative study. A nonsynonymous single nucleotide polymorphism (SNP) rs1545620 at the 3' end of the gene was found to be significantly associated with UC and weakly associated with Crohn's disease (CD). The aim of our current study was to replicate these findings in an independent UC cohort and to investigate association with CD. We also investigated subphenotype association and interactions with CARD15, IL23R, ATG16L1, and the IBD5 risk haplotype.


METHODS
In all, 652 CD patients, 650 UC patients, and 1190 controls were genotyped for 8 MYO9B SNPs. Haplotype testing, epistasis testing with known polymorphisms, and subphenotype analysis were performed.


RESULTS
An intronic SNP rs2305767 in the MYO9B gene was associated with inflammatory bowel disease (IBD) overall (corrected P-value 0.002, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.67-0.86). On individual disease analysis an association was found with CD (corrected P-value 0.001, OR 0.62, 95% CI 0.53-0.73) but not with UC. Analysis of the common MYO9B haplotypes showed significant association for CD and UC alone and IBD overall. No subphenotypic association was found. These data support an association between CD and SNPs in MYO9B independent of the established effects of SNPs in CARD15, IL23R, ATG16L1, and the IBD5 haplotype. There was no evidence of epistasis between SNPs in MYO9B and these established genes.


CONCLUSIONS
MYO9B variants may be involved in IBD pathogenesis.
Cooney
Rachel
R
Wellcome Trust Centre of Human Genetics, University of Oxford, Oxford, UK. rachel.cooney@ndm.ox.ac.uk
Cummings
J R Fraser
JR
Pathan
Saad
S
Beckly
John
J
Geremia
Alessandra
A
Hancock
Laura
L
Guo
Changcun
C
Morris
Andrew
A
Jewell
Derek P
DP
D000293:Adolescent; D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009218:Myosins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; C113469:myosin IXB; D009218:Myosins