Pathway Analysis for Genome-Wide Association Study of Basal Cell Carcinoma of the Skin 英文参考文献.docVIP

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Pathway Analysis for Genome-Wide Association Study of Basal Cell Carcinoma of the Skin 英文参考文献.doc

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Pathway Analysis for Genome-Wide Association Study of Basal Cell Carcinoma of the Skin 英文参考文献

PathwayAnalysisforGenome-WideAssociationStudyof BasalCellCarcinomaoftheSkin MingfengZhang1,2*,LimingLiang3,4,MoushengXu4,AbrarA.Qureshi1,5,JialiHan1,4,5 1Department of Dermatology, Clinical Research Program, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2DepartmentofEpidemiologyandBiostatistics,CancerCenter,NanjingMedicalUniversity,Nanjing,China,3DepartmentofBiostatistics,HarvardSchoolofPublicHealth, Boston, Massachusetts, United States of America, 4Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 5ChanningLaboratory,DepartmentofMedicine,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract Background: Recently, a pathway-based approach has been developed to evaluate the cumulative contribution of the functionallyrelatedgenesforgenome-wideassociationstudies(GWASs),whichmayhelputilizeGWASdatatoagreater extent. Methods:Inthisstudy,weappliedthisapproachfortheGWASofbasalcellcarcinoma(BCC)oftheskin.Wefirstconducted theBCCGWASamong1,797BCCcasesand5,197controlsinCaucasianswith740,760genotypedSNPs.115,688SNPswere grouped into gene transcripts within 20kb in distance and then into 174 Kyoto Encyclopedia of Genes and Genomes pathways,205BioCartapathways,aswellastwopositivecontrolgenesets(pigmentationgenesetandBCCriskgeneset). TheassociationofeachpathwaywithBCCriskwasevaluatedusingtheweightedKolmogorov-Smirnovtest.Onethousand permutationswereconductedtoassessthesignificance. Results:Bothofthepositivecontrolgenesetsreachedpathwayp-values,0.05.Fourotherpathwayswerealsosignificantly associated with BCC risk: the heparan sulfate biosynthesis pathway (p = 0.007, false discovery rate, FDR = 0.35), the mCalpainpathway(p = 0.002,FDR = 0.12),theRhocellmotilitysignalingpathway(p = 0.011,FDR = 0.30),andthenitric oxidepathway(p = 0.022,FDR = 0.42). Conclusion:WeidentifiedfourpathwaysassociatedwithBCCrisk,whichmayoffernewin