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 Lin; Nadia 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

doi:10.1038/s41467-019-08923-6

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 Lin

Nadia 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 language	English
Article number	1052
Number of pages	12
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-08923-6
Publication status	Published - 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, Article 1052. https://doi.org/10.1038/s41467-019-08923-6

@article{1b33ad549370408d8c174905e1f4ddf8,

title = "Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci",

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.",

author = "\{the 23 and Me Research Team\} and Tom Dudding and Simon Haworth and Lind, \{Penelope A.\} and Sathirapongsasuti, \{J. Fah\} and Michelle Agee and Babak Alipanahi and Adam Auton and Bell, \{Robert K.\} and Katarzyna Bryc and Elson, \{Sarah L.\} and Pierre Fontanillas and Furlotte, \{Nicholas A.\} and Barry Hicks and Hinds, \{David A.\} and Huber, \{Karen E.\} and Jewett, \{Ethan M.\} and Yunxuan Jiang and Aaron Kleinman 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 Suyash Shringarpure and Chao Tian and Vladimir Vacic and Xin Wang and Wilson, \{Catherine H\} and Tung, \{Joyce Y.\} and Ruth Mitchell and Luc{\'i}a Colodro-Conde and Medland, \{Sarah E.\} and Scott Gordon and Benjamin Elsworth and Lavinia Paternoster and Franks, \{Paul W.\} and Thomas, \{Steven J.\} and Martin, \{Nicholas G.\} and Timpson, \{Nicholas J.\}",

year = "2019",

month = mar,

day = "5",

doi = "10.1038/s41467-019-08923-6",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

the 23 and Me Research Team, Dudding, T , Haworth, S, Lind, PA, Sathirapongsasuti, JF, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, Hicks, B, Hinds, DA, Huber, KE, Jewett, EM, Jiang, Y, Kleinman, A, Lin, KH, Litterman, NK, McCeight, JC, McIntyre, MH, McManus, KF, Mountain, JL, Noblin, ES, Northover, CAM, Pitts, SJ, Poznik, GD, Shelton, JF, Shringarpure, S, Tian, C, Vacic, V, Wang, X, Wilson, CH, Tung, JY, Mitchell, R, Colodro-Conde, L, Medland, SE, Gordon, S, Elsworth, B, Paternoster, L, Franks, PW, Thomas, SJ, Martin, NG & Timpson, NJ 2019, 'Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci', Nature Communications, vol. 10, 1052. https://doi.org/10.1038/s41467-019-08923-6

TY - JOUR

T1 - Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci

AU - the 23 and Me Research Team

AU - Dudding, Tom

AU - Haworth, Simon

AU - Lind, Penelope A.

AU - Sathirapongsasuti, J. Fah

AU - Agee, Michelle

AU - Alipanahi, Babak

AU - Auton, Adam

AU - Bell, Robert K.

AU - Bryc, Katarzyna

AU - Elson, Sarah L.

AU - Fontanillas, Pierre

AU - Furlotte, Nicholas A.

AU - Hicks, Barry

AU - Hinds, David A.

AU - Huber, Karen E.

AU - Jewett, Ethan M.

AU - Jiang, Yunxuan

AU - Kleinman, Aaron

AU - Lin, Keng Han

AU - Litterman, Nadia K.

AU - McCeight, Jennifer C.

AU - McIntyre, Matthew H.

AU - McManus, Kimberly F.

AU - Mountain, Joanna L.

AU - Noblin, Elizabeth S.

AU - Northover, Carrie A.M.

AU - Pitts, Steven J.

AU - Poznik, G. David

AU - Shelton, Janie F.

AU - Shringarpure, Suyash

AU - Tian, Chao

AU - Vacic, Vladimir

AU - Wang, Xin

AU - Wilson, Catherine H

AU - Tung, Joyce Y.

AU - Mitchell, Ruth

AU - Colodro-Conde, Lucía

AU - Medland, Sarah E.

AU - Gordon, Scott

AU - Elsworth, Benjamin

AU - Paternoster, Lavinia

AU - Franks, Paul W.

AU - Thomas, Steven J.

AU - Martin, Nicholas G.

AU - Timpson, Nicholas J.

PY - 2019/3/5

Y1 - 2019/3/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85062587642

U2 - 10.1038/s41467-019-08923-6

DO - 10.1038/s41467-019-08923-6

M3 - Article (Academic Journal)

C2 - 30837455

AN - SCOPUS:85062587642

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

M1 - 1052

ER -

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

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GWAS summary statistics for mouth ulcers

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

Abstract

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GWAS summary statistics for mouth ulcers

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