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An Integrated Proteome and Transcriptome Analysis Identifies Novel Causal Genes in Periodontal Disease
38 Pages Posted: 31 Jan 2023
More...Abstract
Background: Periodontal disease (PD) has been linked to several SNP loci by genomewide association studies (GWAS). It is still unclear how these loci contribute to periodontal disease and what the most effective drug targets are for treating it. We, therefore, sought to identify genes responsible for PD's pathogenesis.
Methods: By integrating multidimensionality and high throughput data, the proteome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and Bayesian colocalization analysis were employed to screen candidate genes that bring about PD risk via influencing their expression and protein abundance in the blood.
Findings: Our comprehensive analysis demonstrated that the protein abundance of 56 genes was associated with periodontal disease in line accordance with robust evidence at the protein level. Five candidate genes (NAP1L4, ADAMTS5, SIGLEC14, TAPBP, and DARS) were validated for TWAS. After combining Mendelian randomization with Bayesian colocalization analysis, we identified five genes associated with periodontal disease (HBZ, NAP1L4, GLRX, ADAMTS5, and SIGLEC12).
Interpretations: Multidimensional data analysis enabled us to prioritize causal genes in PD pathogenesis, providing insight into future research.
Funding: The work was supported by the National Natural Science Foundation of China (No:82060498).
Declaration of Interest: The authors declare that they have no competing interests.
Keywords: Periodontal disease, Proteome-wide association study, transcriptome-wide association study, mendelian randomization, Bayesian colocalization, Causality
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