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

the 23 and Me Research Team, Tom Dudding, Simon Haworth, Penelope A. Lind, J. Fah Sathirapongsasuti, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Barry Hicks, David A. Hinds, Karen E. Huber, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Keng Han LinNadia K. Litterman, Jennifer C. McCeight, Matthew H. McIntyre, Kimberly F. McManus, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A.M. Northover, Steven J. Pitts, G. David Poznik, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Vladimir Vacic, Xin Wang, Catherine H Wilson, Joyce Y. Tung, Ruth Mitchell, Lucía Colodro-Conde, Sarah E. Medland, Scott Gordon, Benjamin Elsworth, Lavinia Paternoster, Paul W. Franks, Steven J. Thomas, Nicholas G. Martin, Nicholas J. Timpson*

*Corresponding author for this work

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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 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.

Original languageEnglish
Article number1052
Number of pages12
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 5 Mar 2019

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    the 23 and Me Research Team, Dudding, T., Haworth, S., Lind, P. A., Sathirapongsasuti, J. F., Agee, M., Alipanahi, B., Auton, A., Bell, R. K., Bryc, K., Elson, S. L., Fontanillas, P., Furlotte, N. A., Hicks, B., Hinds, D. A., Huber, K. E., Jewett, E. M., Jiang, Y., Kleinman, A., ... Timpson, N. J. (2019). Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci. Nature Communications, 10, [1052]. https://doi.org/10.1038/s41467-019-08923-6