Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources 英文参考文献.docVIP

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Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources 英文参考文献.doc

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Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources 英文参考文献

PrioritizationandEvaluationofDepressionCandidate GenesbyCombiningMultidimensionalDataResources Chung-FengKao1,Yu-ShengFang2,ZhongmingZhao3,Po-HsiuKuo1,2,4* 1DepartmentofPublicHealthandInstituteofEpidemiologyandPreventiveMedicine,CollegeofPublicHealth,NationalTaiwanUniversity,Taipei,Taiwan,2Instituteof Clinical Medicine,School ofMedicine,NationalCheng-KungUniversity,Tainan, Taiwan, 3Departments ofBiomedicalInformatics andPsychiatry,Vanderbilt University School ofMedicine,Nashville,Tennessee,UnitedStates ofAmerica,4ResearchCenterfor Genes, Environment andHumanHealth,NationalTaiwanUniversity,Taipei, Taiwan Abstract Background:Largescaleandindividualgeneticstudieshavesuggestednumeroussusceptiblegenesfordepressioninthe pastdecadewithoutconclusiveresults.Thereisastrongneedtoreviewandintegratemulti-dimensionaldataforfollowup validation. The present study aimed to apply prioritization procedures to build-up an evidence-based candidate genes datasetfordepression. Methods: Depression candidate genes were collected in human and animal studies across various data resources. Each gene was scored according to its magnitude of evidence related to depression and was multiplied by a source-specific weighttoformacombinedscoremeasure.Allgeneswereevaluatedthroughaprioritizationsystemtoobtainanoptimal weightmatrixtoranktheirrelativeimportancewithdepressionusingthecombinedscores.Theresultingcandidategene list for depression (DEPgenes) was further evaluated by a genome-wide association (GWA) dataset and microarray gene expressioninhumantissues. Results: A total of 5,055 candidate genes (4,850 genes from human and 387 genes from animal studies with 182 being overlapped)wereincluded fromsevendatasources.Throughtheprioritization procedures,weidentified169DEPgenes, which exhibited high chance to be associated with depression in GWA dataset (Wilcoxon rank-sum test, p =0.00005). Additionally,theDEPgeneshadahigherpercentagetoexpressinhumanbrainornerverelatedtissuesthannon-DEPgenes,