title: Association signals unveiled by a comprehensive gene set enrichment analysis of dental caries genome-wide association studies.
abstract: Gene set-based analysis of genome-wide association study (GWAS) data has recently emerged as a useful approach to examine the joint effects of multiple risk loci in complex human diseases or phenotypes. Dental caries is a common, chronic, and complex disease leading to a decrease in quality of life worldwide. In this study, we applied the approaches of gene set enrichment analysis to a major dental caries GWAS dataset, which consists of 537 cases and 605 controls. Using four complementary gene set analysis methods, we analyzed 1331 Gene Ontology (GO) terms collected from the Molecular Signatures Database (MSigDB). Setting false discovery rate (FDR) threshold as 0.05, we identified 13 significantly associated GO terms. Additionally, 17 terms were further included as marginally associated because they were top ranked by each method, although their FDR is higher than 0.05. In total, we identified 30 promising GO terms, including 'Sphingoid metabolic process,' 'Ubiquitin protein ligase activity,' 'Regulation of cytokine secretion,' and 'Ceramide metabolic process.' These GO terms encompass broad functions that potentially interact and contribute to the oral immune response related to caries development, which have not been reported in the standard single marker based analysis. Collectively, our gene set enrichment analysis provided complementary insights into the molecular mechanisms and polygenic interactions in dental caries, revealing promising association signals that could not be detected through single marker analysis of GWAS data.
authors: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Quan
authors: Q
authors: Wang
authors: Peilin
authors: P
authors: Jia
authors: Karen T
authors: KT
authors: Cuenco
authors: Zhen
authors: Z
authors: Zeng
authors: Eleanor
authors: E
authors: Feingold
authors: Mary L
authors: ML
authors: Marazita
authors: Lily
authors: L
authors: Wang
authors: Zhongming
authors: Z
authors: Zhao
mesh_terms: D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D030541:Databases, Genetic; D003731:Dental Caries / Q000235:genetics*; D005260:Female; D063990:Gene Ontology; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide
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