Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease and Edentulism in the Atherosclerosis Risk in Communities Study

Authors

Naisi Zhao
Flavia Teles
Jiayun Lu
Devin C Koestler
James Beck
Eric Boerwinkle
Jan Bressler
Karl T Kelsey
Elizabeth A Platz
Dominique S Michaud

Publication Date

9-1-2023

Journal

Journal of Clinical Periodotology

Abstract

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that was significantly hypomethylated in severe periodontal disease compared with no/mild periodontal disease in European American participants. Higher methylation levels in a separate region in an unknown gene (located in Chr10: 743,992-744,958) was associated with significantly higher odds of edentulism compared with no/mild periodontal disease in African American participants. In subsequent CpG testing, four CpGs in a region previously associated with periodontitis located within HOXA4 were significantly hypermethylated in severe periodontal disease compared with no/mild periodontal disease in African American participants (odds ratio per 1 SD increase in methylation level: cg11015251: 1.28 (1.02, 1.61); cg14359292: 1.24 (1.01, 1.54); cg07317062: 1.30 (1.05, 1.61); cg08657492: 1.25 (1.01, 1.55)).

CONCLUSIONS: Our study highlights epigenetic variations in ZPF57 and HOXA4 that were significantly and reproducibly associated with periodontitis. Future studies should evaluate gene regulatory mechanisms in the candidate regions of these loci.

Keywords

Periodontitis, periodontal disease, DNA methylation, Illumina Infinium HumanMethylation450K, epigenome-wide association study (EWAS), peripheral blood

Comments

Supplementary Materials

PMID: 37464577