The integration of transcriptome-wide association study and mRNA expression profiling data to identify candidate genes and gene sets associated with dental caries. (October 2020)

• Record Type: Journal Article
• Authors: Tong, Xiangyao; Hou, Siyu; Ma, Mei; Zhang, Lu; Zou, Rui; Hou, Tiezhou; Niu, Lin
• Is Part Of: Archives of oral biology. Volume 118(2020)
• Publication Date: 2020-10
• Subjects: GWAS genome-wide association study -- TWAS transcriptome-wide association study -- GO gene ontology -- IL32 interleukin 32 -- GALK2 galactokinase 2 -- CELF4 CUGBP, Elav-like family member 4 -- BCOR BCL6 corepressor -- BCORL1 BCL6 corepressor like 1 -- INHBA inhibin subunit beta A -- CXCR C-X-C motif chemokine receptor -- NAMPT nicotinamide phosphoribosyltransferase -- BMP7 bone morphogenetic protein 7 -- GLIDE Gene-Lifestyle Interactions in Dental Endpoints -- SNPs single-nucleotide polymorphisms -- mRNA messenger RNA -- DAVID Database for Annotation, Visualization and Integrated Discovery -- ICD-10 International Classification of Diseases-10 -- PCA Principal component analysis -- LD linkage disequilibrium -- A4GALT alpha 1, 4-galactosyltransferase -- TIE1 tyrosine kinase with immunoglobulin like and EGF like domains 1 -- ASNS asparagine synthetase (glutamine-hydrolyzing) -- IVNS1ABP influenza virus NS1A binding protein -- SCFD1 sec1 family domain containing 1 -- PTCD3 pentatricopeptide repeat domain 3 -- AATF apoptosis antagonizing transcription factor -- CAPZA2 capping actin protein of muscle Z-line subunit alpha 2 -- CTSC cathepsin C -- STAB1 stabilin 1 -- NCF2 neutrophil cytosolic factor 2 -- eQTLs expression quantitative traits loci -- meQTL methylation quantitative traits loci -- PLS Papillon Lefevre syndrome -- ROS reactive oxygen species -- TLR4 toll-like receptor 4 -- DPSCs dental pulp stem cells -- LPS Lipopolysaccharide -- PD-L1 Programmed cell death 1 ligand 1; Dental caries -- Genome-wide association study (GWAS) -- Transcriptome-wide association study (TWAS) -- Gene expression profiling; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2020.104863
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: TWAS identified 503 genes associated with the susceptibility to dental caries. We identified 6 common candidate genes and 5 common GO terms associated with dental caries. Our study results may provide novel clues for understanding the genetic mechanisms of dental caries. Abstract: Objective: The aim of this study was to identify candidate genes and gene sets associated with dental caries by an integrative analysis of transcriptome-wide association study (TWAS) and messenger RNA (mRNA) expression profiling of dental caries. Methods: A genome-wide association study (GWAS) dataset of dental caries was obtained from the UK Biobank. A TWAS of dental caries was conducted with the FUSION tool using the gene expression reference weights of musculoskeletal, whole blood, and peripheral blood genes. The dental caries-associated genes identified by the TWAS were further subjected to gene ontology (GO) and pathway enrichment analyses to explore dental caries-related gene sets. Finally, the TWAS results of dental caries were compared with genome-wide mRNA expression profiling of dental caries to detect common genes and gene sets. Results: The TWAS identified 165 musculoskeletal genes, 110 whole blood genes, and 228 peripheral blood genes. GO analysis of the genes identified by the TWAS detected 57 GO terms. For pathway enrichment analysis, we detected 12 candidate pathways. After comparing the TWAS-identified genes with the mRNA expression profiling data, we detected 6 common genes. Further comparing the GO results of the TWAS and mRNA expression profiling identified 5 common GO terms. Conclusion: We identified a group of dental caries-associated genes and GO terms, providing novel clues for understanding the genetic mechanisms of dental caries.