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

• DOI: 10.1038/s41467-019-08923-6
• Publication Date: 2019-03-05T11:05:48Z
• Authors: Tom Dudding; Simon Haworth; Penelope A. Lind; J. Fah Sathirapon...; ; 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 Lin; Nadia K. Litterman; Jennifer C. McCeight; Matthew H. McIntyre; Kimberly F. McManus; Joanna L. Mountain; Elizabeth S. Noblin; Carrie A. M. Nort...; 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
• Keywords: Adult; Male; 0301 basic medicine; 1300 Biochemistry; Science; T-Lymphocytes; General Physics and Astronomy; 610; Genetics and Molecular Biology; Article; Medical Genetics and Genomics; Cohort Studies; 03 medical and health sciences; 616; Humans; Immunologic Factors; 3100 Physics and Astronomy; Computer Simulation; Genetic Predisposition to Disease; Oral Ulcer; Aged; Q; General Chemistry; Middle Aged; 1600 Chemistry; Medicinsk genetik och genomik; 3. Good health; Genetic Loci; General Biochemistry; Female; Stomatitis, Aphthous; Genome-Wide Association Study

AbstractMouth 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, nearIL12A, 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.