Identifying Shared Key Genes and Cellular Characteristics Between Chronic Periodontitis and Aging Using Integrative Single‐Cell and Mendelian Randomization Analyses

OBJECTIVE: The purpose was to investigate the shared key genes between chronic periodontitis (CP) and aging. MATERIALS AND METHODS: First, we collected single-cell RNA sequencing (scRNA-seq) data of peripheral blood samples from patients with CP, aging, and healthy control (HC) and confirmed the cross-group coexpressed and downregulated cell subsets as the core research objects. Subsequently, we explored the dynamic evolutionary rules and functional interaction patterns of these cell subsets by integrating pseudotime trajectory analysis and intercellular communication modeling. Then, we screened the differentially expressed gene targets and adopted mendelian randomization (MR) analysis to clarify causal association between aging and CP susceptibility. Finally, we performed colocalization analysis by integrating data from CP genome-wide association studies (GWAS) and expression quantitative trait locus datasets and conducted metabolic pathway enrichment analysis on the key genes obtained. RESULTS: Subsets of T cells were found to account for a significant proportion in both CP patients and aging individuals. CD8_CM cells showed a downward trend in these two groups, screening of 16 differentially expressed genes. MR indicated that GZMK, KLRG1, and LYAR had causal relationships and were retained in the validation phase, and colocalization analysis yielded limited evidence supporting the existence of shared causal variants. Furthermore, metabolic enrichment analysis delineated the metabolic pathways functionally associated with these genes. CONCLUSION: This study found the downregulation of CD8_CM cells is a shared feature of CP and aging, and pointed out that GZMK, KLRG1 and LYAR may be the molecular links, offering an innovative perspective on elucidating the intersection mechanisms underlying aging and CP.