Objectives: To study the relation between host transcriptomic and DNA methylation changes in periodontally diseased versus healthy gingival tissues. Materials and Methods: Gingival tissues from 20 chronic periodontitis patients were collected during osseous surgery from diseased and healthy sites. Samples were homogenized and split into two aliquots: One aliquot for RNA sequencing and one for DNA methylation analysis. Results: Periodontal findings: PD averaged 5.5 mm in disease sites vs. 2.7 mm in control sites (p<0.001), clinical attachment level in disease was 5.8 mm vs. 3.1 mm in control (p<0.001). RNA sequencing data: 20 genes were found to be upregulated, and 9 genes were down regulated between similarly performing sample-pairs in pairwise comparison. Methylation data: Within the common differentially expressed genes, 4 genes were overexpressed and hypomethylated. These genes were TIGIT, MS4A1, ICOS and CD22. Further analysis of these genes revealed that they all participate in B-cell or T-cell regulation. Functional analysis: Functional analysis was carried out by IPA which showed that Th2 and T-cell receptor signaling pathways were mostly affected by differentially expressed genes. Moreover, stratified analysis on demography showed African-American had a propensity to show similar trends in terms of differential expression of genes and differential DNA methylation when compared to the Caucasian. Conclusions: Epigenome Wide Association Studies of gingival tissues transcriptome and methylome are useful for screening for biomarker candidates for chronic periodontitis. TIGIT, MS4A1, ICOS and CD22 genes are potential candidate biomarkers for chronic periodontitis. Further validation of these biomarkers using in vivo functional studies is necessary.