Year: 2019
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: 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
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,108
Funders: Wellcome Trust, QIMR Berghofer Medical Research Institute, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Diabetes UK, University of Bristol, Northwest Regional Development Agency, National Institutes of Health, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse
Awards: G1131969086, G1192034430, The Genetics of Vulnerability to Nicotine Addictions, G1436884665, G1605161196, Validation and Replication of Genes Associated with Common Human Disease Using Australian Twin Families, G173885373, G1853612974, Advancing our understanding of the genetics of Psychiatric and Neurological Disease, G1935686924, Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis, G1987169411, G235045266, G2466259667, G2624192138, G2642749895, G2952053418, Molecular Epidemiology of Alcoholism 3 - EDAC Families, G3199409182, G3209059653, G3288322216, G3344456887, G3345452146, Identification of genetic risk factors for asthma: genome-wide association and the role of epigenetics, G3831911591, G3862454230, Genome-wide combined linkage-association scan of multiply phenotyped twin sibships, Pigmentation genes and melanoma risk, G4337057405, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., Genetics and prediction of complex disease risk, Association Screen of Migraine Candidate Genes, G4603568690, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G4815361747, Molecular Epidemiology of Alcoholism 1: Candidate Gene, G5329469444, G5508833615, G5562631338, Mapping Genes for typical migraine using twin families., G6119919417, G6423108142, Genetics of moliness, G6682065591, Develop & improve methodology in gene mapping, targetting localisation of genes underlying migraine & other disorders, Quantitative and Molecular Genetic Analysis of Cognition, Uncoupled Research Fellowship, Genetics of moliness, G6994344002, Molecular Epidemiology of Alcoholism 2- Big Sibships, G7193217417, VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTION, Genetic Epidemiology of Pathological Gambling, G7828794151, G7857206400, Vitamin D and head and neck cancer risk and progression: An examination of causality and mechanisms., G7894417573, Investigating the causal nature of associations between dental disease, cardio-metabolic traits and cardiovascular outcomes: providing evidence for a potential role of dentistry in improving population cardiovascular health., Locating genes for elementary and complex cognitive abilities using genetic linkage and association analysis, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G8284071903, G8378694876, PERSISTENCE AND CHANGE IN DRINKING HABITS--TWIN STUDY, G856913103, THE GENETICS OF VULNERABILITY TO NICOTINE ADDICTIONS, Investigating the causal nature of associations between dental disease, cardio-metabolic traits and cardiovascular outcomes: providing evidence for a potential role of dentistry in improving population cardiovascular health., Statistical Methods and Algorithms for Analysis of High-throughput Genetics and Genomics Platforms, G9000243987
OpenAlex ID: W2920042327