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Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci

Dudding, Tom; Haworth, Simon; Lind, Penelope A.; Sathirapongsasuti, J. Fah; Agee, Michelle; Alipanahi, Babak; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna and Elson, Sarah L., et al. (2019) In Nature Communications 10.
Abstract

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e−483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics... (More)

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e−483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.

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Nature Communications
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10
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Nature Publishing Group
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  • scopus:85062587642
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2041-1723
DOI
10.1038/s41467-019-08923-6
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English
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yes
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6513e690-cce3-4588-a7ec-5bc93b9a5a4f
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2019-03-15 09:24:21
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2019-04-10 04:21:11
@article{6513e690-cce3-4588-a7ec-5bc93b9a5a4f,
  abstract     = {<p>Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e−483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.</p>},
  articleno    = {1052},
  author       = {Dudding, Tom and Haworth, Simon and Lind, Penelope A. and Sathirapongsasuti, J. Fah and Agee, Michelle and Alipanahi, Babak and Auton, Adam and Bell, Robert K. and Bryc, Katarzyna and Elson, Sarah L. and Fontanillas, Pierre and Furlotte, Nicholas A. and Hicks, Barry and Hinds, David A. and Huber, Karen E. and Jewett, Ethan M. and Jiang, Yunxuan and Kleinman, Aaron and Lin, Keng Han and Litterman, Nadia K. and McCeight, Jennifer C. and McIntyre, Matthew H. and McManus, Kimberly F. and Mountain, Joanna L. and Noblin, Elizabeth S. and Northover, Carrie A.M. and Pitts, Steven J. and Poznik, G. David and Shelton, Janie F. and Shringarpure, Suyash and Tian, Chao and Vacic, Vladimir and Wang, Xin and Wilson, Catherine H. and Tung, Joyce Y. and Mitchell, Ruth and Colodro-Conde, Lucía and Medland, Sarah E. and Gordon, Scott and Elsworth, Benjamin and Paternoster, Lavinia and Franks, Paul W. and Thomas, Steven J. and Martin, Nicholas G. and Timpson, Nicholas J.},
  issn         = {2041-1723},
  language     = {eng},
  month        = {03},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci},
  url          = {http://dx.doi.org/10.1038/s41467-019-08923-6},
  volume       = {10},
  year         = {2019},
}