Identification of novel genome-wide pleiotropic associations with oral inflammatory traits.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101093320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1617-4623 (Electronic) Linking ISSN: 16174623 NLM ISO Abbreviation: Mol Genet Genomics Subsets: MEDLINE

Original Publication: Berlin : Springer-Verlag, c2001-

Genetic Pleiotropy*; Mouth Diseases/*genetics ; Stomatitis/*genetics; Cohort Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Inflammation/epidemiology ; Inflammation/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Mouth Diseases/epidemiology ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Stomatitis/epidemiology ; Stomatognathic Diseases/epidemiology ; Stomatognathic Diseases/genetics ; Tripartite Motif Proteins/genetics ; United Kingdom/epidemiology

Oral inflammatory diseases (OIDs) are a group of dental diseases with multiple clinical manifestations that impact the majority of the world's population. Many studies have investigated the associations between individual OID traits and genomic variants, but whether pleiotropic loci are shared by oral inflammatory traits remains poorly understood. Here, we conducted multitrait joint analyses based on the summary statistics of genome-wide association studies (GWASs) of five dental traits from the UK Biobank. Among these genome-wide significant loci, two were novel for both painful gums and toothache. We identified causal variants at each novel locus, and functional annotation based on multiomics data suggested IL10 and IL12A/TRIM59 as potential candidate genes at the novel pleiotropic loci. Subsequent analyses of pathway enrichment and protein-protein interaction networks suggested the involvement of the candidate genes in immune regulation. In conclusion, our results uncover novel pleiotropic loci for OID traits and highlight the importance of immune regulation in the pathogenesis of OIDs. These findings will enhance our understanding of the pathogenesis of OIDs and be beneficial for risk screening, prevention, and the development of novel drugs targeting the immune regulation of OIDs.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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2013KZ118 scientific and technological research grant of tianjin health commission

Keywords: Genome-wide association studies; Immunity; Inflammation; Multitrait joint analysis; Oral diseases; Pleiotropic loci

0 (Intracellular Signaling Peptides and Proteins)
0 (TRIM59 protein, human)
0 (Tripartite Motif Proteins)

Date Created: 20211025 Date Completed: 20220207 Latest Revision: 20220207

20231215

10.1007/s00438-021-01826-6

34694461