Association Signals Unveiled by a Comprehensive Gene Set Enrichment Analysis of Dental Caries Genome-Wide Association Studies

Quan Wang, Peilin Jia, Karen T. Cuenco, Zhen Zeng, Eleanor Feingold, Mary L. Marazita, Lily Wang, Zhongming Zhao

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere72653
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 14 2013
Externally publishedYes

Fingerprint

dental caries
Gene Ontology
Genome-Wide Association Study
Dental Caries
Genes
genes
Chemical Databases
Ontology
Ubiquitin-Protein Ligases
Ceramides
Chronic Disease
complementary genes
Quality of Life
ubiquitin-protein ligase
ceramides
Cytokines
Phenotype
genome-wide association study
quality of life
human diseases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Association Signals Unveiled by a Comprehensive Gene Set Enrichment Analysis of Dental Caries Genome-Wide Association Studies. / Wang, Quan; Jia, Peilin; Cuenco, Karen T.; Zeng, Zhen; Feingold, Eleanor; Marazita, Mary L.; Wang, Lily; Zhao, Zhongming.

In: PLoS One, Vol. 8, No. 8, e72653, 14.08.2013.

Research output: Contribution to journalArticle

Wang, Quan ; Jia, Peilin ; Cuenco, Karen T. ; Zeng, Zhen ; Feingold, Eleanor ; Marazita, Mary L. ; Wang, Lily ; Zhao, Zhongming. / Association Signals Unveiled by a Comprehensive Gene Set Enrichment Analysis of Dental Caries Genome-Wide Association Studies. In: PLoS One. 2013 ; Vol. 8, No. 8.
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