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

AssociationSignalsUnveiledbyaComprehensiveGene SetEnrichmentAnalysisofDentalCariesGenome-Wide AssociationStudies QuanWang1.,PeilinJia1.,KarenT.Cuenco2,3,ZhenZeng4,EleanorFeingold2,4,MaryL.Marazita2,3 LilyWang5,6*,ZhongmingZhao1,6,7,8 , * 1Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 2Department of Human Genetics, UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,3CenterforCraniofacialandDentalGenetics,DepartmentofOralBiology,SchoolofDental Medicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,4DepartmentofBiostatistics,UniversityofPittsburgh,Pittsburgh,Pennsylvania, UnitedStatesofAmerica,5DepartmentofBiostatistics,VanderbiltUniversitySchoolofMedicine,Nashville,Tennessee,UnitedStatesofAmerica,6CenterforQuantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 7Department of Psychiatry, Vanderbilt University School of Medicine, Nashville,Tennessee,UnitedStatesofAmerica,8DepartmentofCancerBiology,VanderbiltUniversitySchoolofMedicine,Nashville,Tennessee,UnitedStatesofAmerica Abstract Gene set-based analysis of genome-wide association study (GWAS) data has recently emerged as a useful approach to examinethejointeffectsofmultiplerisklociincomplexhumandiseasesorphenotypes.Dentalcariesisacommon,chronic, andcomplexdiseaseleadingtoadecreaseinqualityoflifeworldwide.Inthisstudy,weappliedtheapproachesofgeneset 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 SignaturesDatabase(MSigDB).Settingfalsediscoveryrate(FDR)thresholdas0.05,weidentified13significantlyassociated 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