Tensor composition analysis suggests cell-type-specific DNA methylation signatures associated with a self-reported periodontitis-related phenotype and NLRP3 inflammasome-related immune regulatory networks

Periodontitis is a prevalent oral chronic inflammatory disease with systemic repercussions, yet whole blood epigenome-wide association studies (EWAS) are often confounded by leukocyte heterogeneity in both cellular composition and DNA methylation profile. Thus, we sought to resolve cell-type-specific epigenetic signatures associated with a self-reported periodontitis-related phenotype (i.e. self-reported gingival bleeding and tooth mobility) by applying tensor composition analysis (TCA) to isolate neutrophil- and monocyte-specific methylation signals, with a particular focus on genes involved in NLRP3 inflammasome pathways. Inflammasome-related genes were curated from KEGG and prioritized using Endeavour. Raw Illumina IDAT files from periodontitis-related phenotype cases and controls were processed in R, yielding an analytic subset of 73 adults reporting gingival bleeding and tooth mobility. After stringent probe filtering, TCA was used to deconvolute neutrophil and monocyte components. CpG-wise logistic regression on M-values was performed using limma, adjusting for age, sex, smoking status, body mass index, and metabolic disruption; an auxiliary model excluded metabolic covariates to enhance statistical power. Neutrophils from periodontitis-related phenotype cases exhibited differential methylation in immune-response related genes, including hypomethylation of MAP2K1 , HLA - DOA , HLA-DRB1 , HLA-B , and CD1D , and hypermethylation of AD CY9 and BM P7 . Monocytes showed significant hypomethylation in TP73 , IL32 , and COL5A1 . Candidate-guided EWAS coupled with TCA reveals distinct cell-specific epigenetic alterations associated with this self-reported periodontitis-related phenotype, supporting the involvement of an inflammasome-related, immune-regulatory network rather than direct dysregulation of canonical NLRP3 inflammasome genes.