Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis

Abstract

Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis.

Identification of disease-associate variants of aggressive periodontitis using genome-wide association studies

“…The integration of multiple omics datasets, including data obtained from GWAS, can provide a more comprehensive understanding of the disease. Trans-omics analyses enable us to decipher the intricate interplay between genetic and environmental factors, including bacterial factors, which will shed light on novel avenues for therapeutic interventions and personalized treatment approaches [86] , [87] , [88] . For example, mathematical modeling is a complementary tool for studying the pathogenesis of periodontitis.…”