GWAS Helps Uncover the Genomics of Mouth Ulcers

March 5, 2019
GWAS Helps Uncover the Genomics of Mouth Ulcers
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Mouth ulcers or as they are often colloquially referred, canker sores, affect up to 25% of young adults and a higher proportion of children. Many causes of mouth ulcers have been previously identified including mucosal trauma and a range of autoimmune and inflammatory conditions, such as Crohn’s disease, lupus, and ulcerative colitis. Moreover, while earlier research has shown that mouth ulcers are partially heritable until now there has been little evidence linking specific genes or genomic regions to mouth ulcers.

“Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS),” the authors wrote. “Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS.”

Now, a team of investigators led by scientists at the University of Bristol, has identified the areas of the genome associated with triggering mouth ulcers. By analyzing genetic data derived from over 450,000 participants in the UK Biobank over 350,000 participants in USA-based data collection from 23andMe, the research team discovered 97 common genetic variations across the genome that predispose people to mouth ulcers. Findings from the new study were published today in Nature Communications through an article titled “Genome-wide analysis for mouth ulcers identifies associations at immune regulatory loci.”

Additionally, the study went on to look at three further studies, including Bristol’s Children of the 90s (ALSPAC) study, which showed confirmatory results. These variations are enriched in genes that have previously been linked to regulation of the body’s immune system.

“In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%),” the authors stated. “This study finds 97 variants which alter the odds of developing nonspecific 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.”

Lead study investigator Tom Dudding, a doctoral candidate at the University of Bristol, added, “Currently, there are few satisfactory drug treatments for mouth ulcers as current medication options are nonspecific and can lead to side effects. The field has gone from very little genetic understanding of mouth ulcers to having up to 97 areas of the genome which may provide an excellent basis for future research.”

The research team was encouraged by their findings and are looking into drug discovery endeavors that could be helpful in treating these painful sores.

“Importantly, our findings also show that several of the genes related to mouth ulcers are in pathways which are already targeted by drugs that are used to treat other diseases, such as rheumatoid arthritis and psoriasis,” Dudding concluded. There is the potential that drugs like these could be used to treat mouth ulcers, although further work is required to demonstrate this.”