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

Guirong Zhu; Xing Cui; Liwen Fan; Yongchu Pan; Lin Wang

doi:10.3390/cells12010070

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

Cells. 2022 Dec 23;12(1):70. doi: 10.3390/cells12010070.

Authors

Guirong Zhu^{1

2

3}, Xing Cui^{1

2

3}, Liwen Fan^{1

2

3}, Yongchu Pan^{1

2

3

4}, Lin Wang^{1

2

3

4}

Affiliations

¹ Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210029, China.
² Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.
³ Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, China.
⁴ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.

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.

Keywords: genome-wide association study (GWAS); periodontitis; transcriptome-wide association study (TWAS).

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Profiling
Genome-Wide Association Study*
Humans
Quantitative Trait Loci
Transcriptome* / genetics

Grants and funding

This research was funded by the National Natural Science Foundation of China, grant numbers 82270496, 81830031, 81970969, 82001088, and 82101054; and the Priority Academic Program Development of Jiangsu Higher Education Institutions, grant number PAPD-2018-87.