A family-based genome-wide association study of recurrent aphthous stomatitis

Oral Dis. 2020 Nov;26(8):1696-1705. doi: 10.1111/odi.13490. Epub 2020 Jul 30.


Objectives: The aetiology of recurrent aphthous stomatitis (RAS) remains unknown. Individuals may share features of genetic susceptibility, and there may also be a hereditary component. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing RAS, through a family-based genome-wide association study (GWAS).

Subjects and methods: DNA was extracted from buccal swabs of 91 individuals in 16 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (dFAM) was used to derive SNP association values across all chromosomes.

Results: None of the final 288,452 SNPs reached the genome-wide significant threshold of 5 × 10-8 . The most significant pathways were the Ras and PI3K-Akt signalling pathways, pathways in cancer, circadian entrainment and the Rap 1 signalling pathway.

Conclusions: This confirms that RAS is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying RAS and raises the possibility of identifying individuals at risk of acquiring this condition.

Keywords: aphthous stomatitis; genetic association study; genetic linkage; genetics; mouth; mouth mucosa.

MeSH terms

  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Phosphatidylinositol 3-Kinases
  • Polymorphism, Single Nucleotide
  • Stomatitis, Aphthous* / genetics