Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 03 2019
05 03 2019
Historique:
received:
12
10
2018
accepted:
05
02
2019
entrez:
7
3
2019
pubmed:
7
3
2019
medline:
6
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30837455
doi: 10.1038/s41467-019-08923-6
pii: 10.1038/s41467-019-08923-6
pmc: PMC6400940
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1052Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA007535
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA014041
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH066206
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA013321
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA012854
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/3
Pays : United Kingdom
Organisme : NIAAA NIH HHS
ID : R01 AA013320
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA013326
Pays : United States
Organisme : NIDA NIH HHS
ID : R56 DA012854
Pays : United States
Investigateurs
Michelle Agee
(M)
Babak Alipanahi
(B)
Adam Auton
(A)
Robert K Bell
(RK)
Katarzyna Bryc
(K)
Sarah L Elson
(SL)
Pierre Fontanillas
(P)
Nicholas A Furlotte
(NA)
Barry Hicks
(B)
David A Hinds
(DA)
Karen E Huber
(KE)
Ethan M Jewett
(EM)
Yunxuan Jiang
(Y)
Aaron Kleinman
(A)
Keng-Han Lin
(KH)
Nadia K Litterman
(NK)
Jennifer C McCeight
(JC)
Matthew H McIntyre
(MH)
Kimberly F McManus
(KF)
Joanna L Mountain
(JL)
Elizabeth S Noblin
(ES)
Carrie A M Northover
(CAM)
Steven J Pitts
(SJ)
G David Poznik
(GD)
Janie F Shelton
(JF)
Suyash Shringarpure
(S)
Chao Tian
(C)
Vladimir Vacic
(V)
Xin Wang
(X)
Catherine H Wilson
(CH)
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