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| PMID |
|
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| TITLE |
|
| Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci. |
|
| ABSTRACT |
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| 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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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2018/10/12 |
| accepted |
2019/02/05 |
| entrez |
2019/03/07 06:00 |
| pubmed |
2019/03/07 06:00 |
| medline |
2019/04/06 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Dudding T |
|
Dudding |
Tom |
T |
|
Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK. |
| Haworth S |
|
Haworth |
Simon |
S |
|
Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK. |
| Lind PA |
|
Lind |
Penelope A |
PA |
|
Department of Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia. |
| Sathirapongsasuti JF |
|
Sathirapongsasuti |
J Fah |
JF |
|
Research, 23andMe, Inc, Mountain View, 94041, CA, USA. |
|
23andMe Research Team |
|
|
|
|
|
| Tung JY |
|
Tung |
Joyce Y |
JY |
|
Research, 23andMe, Inc, Mountain View, 94041, CA, USA. |
| Mitchell R |
|
Mitchell |
Ruth |
R |
|
Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK. |
| Colodro-Conde L |
|
Colodro-Conde |
Lucía |
L |
|
Department of Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
Department of Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia. |
| Gordon S |
|
Gordon |
Scott |
S |
|
Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia. |
| Elsworth B |
|
Elsworth |
Benjamin |
B |
|
Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK. |
| Paternoster L |
|
Paternoster |
Lavinia |
L |
|
Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK. |
| Franks PW |
|
Franks |
Paul W |
PW |
|
Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, 02115, MA, USA. |
| Thomas SJ |
|
Thomas |
Steven J |
SJ |
|
Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia. |
| Timpson NJ |
|
Timpson |
Nicholas J |
NJ |
|
Medical Research Council Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK. N.J.Timpson@bristol.ac.uk. |
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| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Agee |
Michelle |
M |
|
| Alipanahi |
Babak |
B |
|
| Auton |
Adam |
A |
|
| Bell |
Robert K |
RK |
|
| Bryc |
Katarzyna |
K |
|
| Elson |
Sarah L |
SL |
|
| Fontanillas |
Pierre |
P |
|
| Furlotte |
Nicholas A |
NA |
|
| Hicks |
Barry |
B |
|
| Hinds |
David A |
DA |
|
| Huber |
Karen E |
KE |
|
| Jewett |
Ethan M |
EM |
|
| Jiang |
Yunxuan |
Y |
|
| Kleinman |
Aaron |
A |
|
| Lin |
Keng-Han |
KH |
|
| Litterman |
Nadia K |
NK |
|
| McCeight |
Jennifer C |
JC |
|
| McIntyre |
Matthew H |
MH |
|
| McManus |
Kimberly F |
KF |
|
| Mountain |
Joanna L |
JL |
|
| Noblin |
Elizabeth S |
ES |
|
| Northover |
Carrie A M |
CAM |
|
| Pitts |
Steven J |
SJ |
|
| Poznik |
G David |
GD |
|
| Shelton |
Janie F |
JF |
|
| Shringarpure |
Suyash |
S |
|
| Tian |
Chao |
C |
|
| Vacic |
Vladimir |
V |
|
| Wang |
Xin |
X |
|
| Wilson |
Catherine H |
CH |
|
|
| JOURNAL |
|
| VOLUME: 10 |
| ISSUE: 1 |
| TITLE: Nature communications |
| ISOABBREVIATION: Nat Commun |
| YEAR: 2019 |
| MONTH: 03 |
| DAY: 05 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2041-1723 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
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| MEDLINETA: Nat Commun |
| COUNTRY: England |
| ISSNLINKING: 2041-1723 |
| NLMUNIQUEID: 101528555 |
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| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| R01 AA007535 |
NIAAA NIH HHS |
United States |
| R01 AA014041 |
NIAAA NIH HHS |
United States |
| R01 MH066206 |
NIMH NIH HHS |
United States |
| MC_UU_12013/3 |
Medical Research Council |
United Kingdom |
| R01 AA013321 |
NIAAA NIH HHS |
United States |
| R01 DA012854 |
NIDA NIH HHS |
United States |
|
Wellcome Trust |
United Kingdom |
| R01 AA013320 |
NIAAA NIH HHS |
United States |
| R01 AA013326 |
NIAAA NIH HHS |
United States |
| R56 DA012854 |
NIDA NIH HHS |
United States |
|
| GENERAL NOTE |
|
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| KEYWORDS |
|
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Aged |
|
| Cohort Studies |
|
| Computer Simulation |
|
| Female |
|
| Genetic Loci |
immunology |
| Genetic Predisposition to Disease |
immunology |
| Genome-Wide Association Study |
immunology |
| Humans |
immunology |
| Immunologic Factors |
immunology |
| Male |
immunology |
| Middle Aged |
immunology |
| Oral Ulcer |
immunology |
| Stomatitis, Aphthous |
immunology |
| T-Lymphocytes |
immunology |
|
| SUPPLEMENTARY MESH |
|
| SUPPLMESHNAME |
SUPPLMESHTYPE |
| Sutton disease 2 |
Disease |
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Immunologic Factors |
|
| OTHER ID's |
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|
