Association between genetic variants in myosin IXB and Crohn's disease

Rachel Cooney, J. R Fraser Cummings, Saad Pathan, John Beckly, Alessandra Geremia, Laura Hancock, Changcun Guo, Andrew Morris, Derek P. Jewell

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)1014-1021
Number of pages8
JournalInflammatory Bowel Diseases
Volume15
Issue number7
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Ulcerative Colitis
Crohn Disease
Single Nucleotide Polymorphism
Haplotypes
Inflammatory Bowel Diseases
Odds Ratio
Confidence Intervals
Genes
myosin IXB

Keywords

  • Crohn's disease
  • Epistasis
  • MYO9B
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Cooney, R., Cummings, J. R. F., Pathan, S., Beckly, J., Geremia, A., Hancock, L., ... Jewell, D. P. (2009). Association between genetic variants in myosin IXB and Crohn's disease. Inflammatory Bowel Diseases, 15(7), 1014-1021. https://doi.org/10.1002/ibd.20885

Association between genetic variants in myosin IXB and Crohn's disease. / Cooney, Rachel; Cummings, J. R Fraser; Pathan, Saad; Beckly, John; Geremia, Alessandra; Hancock, Laura; Guo, Changcun; Morris, Andrew; Jewell, Derek P.

In: Inflammatory Bowel Diseases, Vol. 15, No. 7, 2009, p. 1014-1021.

Research output: Contribution to journalArticle

Cooney, R, Cummings, JRF, Pathan, S, Beckly, J, Geremia, A, Hancock, L, Guo, C, Morris, A & Jewell, DP 2009, 'Association between genetic variants in myosin IXB and Crohn's disease', Inflammatory Bowel Diseases, vol. 15, no. 7, pp. 1014-1021. https://doi.org/10.1002/ibd.20885
Cooney R, Cummings JRF, Pathan S, Beckly J, Geremia A, Hancock L et al. Association between genetic variants in myosin IXB and Crohn's disease. Inflammatory Bowel Diseases. 2009;15(7):1014-1021. https://doi.org/10.1002/ibd.20885
Cooney, Rachel ; Cummings, J. R Fraser ; Pathan, Saad ; Beckly, John ; Geremia, Alessandra ; Hancock, Laura ; Guo, Changcun ; Morris, Andrew ; Jewell, Derek P. / Association between genetic variants in myosin IXB and Crohn's disease. In: Inflammatory Bowel Diseases. 2009 ; Vol. 15, No. 7. pp. 1014-1021.
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abstract = "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",
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AU - Cooney, Rachel

AU - Cummings, J. R Fraser

AU - Pathan, Saad

AU - Beckly, John

AU - Geremia, Alessandra

AU - Hancock, Laura

AU - Guo, Changcun

AU - Morris, Andrew

AU - Jewell, Derek P.

PY - 2009

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N2 - 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

AB - 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

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