szdb a database for schizophrenia genetic research 2016 yong wu资料.pdf

该【szdb a database for schizophrenia genetic research 2016 yong wu资料 】是由【小舍儿】上传分享，beplayapp体育下载一共【13】页，该beplayapp体育下载可以免费在线阅读，需要了解更多关于【szdb a database for schizophrenia genetic research 2016 yong wu资料 】的内容，可以使用beplayapp体育下载的站内搜索功能，选择自己适合的beplayapp体育下载，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此beplayapp体育下载到您的设备，方便您编辑和打印。:..esspublishedJuly22,2016SchizophreniaBulletindoi::A?icResearchYong?Wu1,2,Yong-Gang?Yao1–4,andXiong-Jian?Luo*,1,2,41KeyLaboratoryofAnimalModelsandHumanDiseaseMechanismsoftheChineseAcademyofSciencesandYunnanProvince,KunmingInstituteofZoology,Kunming,China;2KunmingCollegeofLifeScience,UniversityofChineseAcademyofSciences,Kunming,China;3CASCenterforExcellenceinBrainScienceandIntelligenceTechnology,ChineseAcademyofSciences,Shanghai,ChinaDownloadedfrom4YGYandXJLareco-correspondingauthorswhojointlydirectedthiswork.*Towhomcorrespondenceshouldbeaddressed;KunmingInstituteofZoology,ChineseAcademyofSciences,Kunming,Yunnan650223,China;tel:?+86-871-68125413,fax:+86-871-68125413,e-mail:******@://schizophreniabulletin./Schizophrenia(SZ),especiallySchizophrenia(SZ)isaseverementaldisordercharac-recentgenome-wideassociationstudies(GWAS),haveterizedbyabnormalperceptions,incoherentorillogi-identifiedmultiplevariants(loci),,%–1%oftheworldpopulationsicfindingsofSZremainsa2–-Withthesubstantialmorbidityandhighmortality,SZplelayersofdatafromvarioussources,eg,icfindingsimposesprofoundimpactonpatients’qualityoflife,andfromGWAS,Vs),associa-,geneexpression,protein–proteinestimatedthattheoverallcostofSZintheUnitedStatesinteraction(PPI),co-expression,expressionquantitative5in2002was$,thetotalcostoftraitloci(eQTL),(Canadiandollars)inatUniversityofNottinghamonJuly26,2016(ENCODE)data,-increasing,whichmakesSZanurgentglobalhealth?(/),acomprehensiveSZandthesubstantialpersonalandsocietalcosts,,geneexpres-availableantipsychoticmedicationscanonlyalleviatethework-baseddata,braineQTLdata,,theefficacyofantipsychoticSNPfunctionannotationinformationweresystematicallydrugsvariesgreatlyamongpatients(ie,manypatientsareextracted,-depthanaly-7,8treatment-resistant).Sofar,?keyreasonforthistherapeu-typesofdatafromvariouslayersofSZresearchweresys--,-expressedinhumanbrainbeenachieved,-friendlySZDBprovidesicandenvironmentalfactorsareinvolvedinhigh-,SZDBpro-plica-oolsfordatasearchandbrowse,tions,exposuretoinfluenzavirusesduringgestation,anddataintegration,–15ThoughenvironmentalfactorshavearoleintheKeywords:schizophrenia/icstudy/database/genepathogenesisofSZ,highheritabilityclearlyshowstheexpression/integrativeanalysis?,pleaseemail:journals.******@Page1of13:..?,,twinandadoptionstudieshaveconsis-monpolygenicvariationcontrib-,,,-Thus,work-,largeinSZandhelpswithmechanisminvestigationanddrugnumbersoflinkageandassociationstudies,-meta-analyseshavebeenperformed,icvariants,genes,andchromosomalregionshavebeenfindingsintomolecularriskmechanismsforSZ,wedevel-–20DespitethefactopedSZDB,acomprehensivedatabasecontainingmul-thatmanypromisingcandidategeneshavebeenidenti-icfied,thesamplesizesarerelativelysmallandthecover--friendlywebDownloadedfromicmarkersarerelativelylowinthesestudies,interfacefordatasearch,browseandvisualize,butalsowhichlimitedtheidentificationofcrediblesusceptibilityprovidesin--wideassocia-suchasSNPfunctionalannotation,spatio-temporalgenetionstudies(GWAS)providescriticalopportunitiestoexpressionpatternanalysisinhumanbrain,,ZNF804Aquantitativetraitloci(eQTL)work-based(PPIhttp://schizophreniabulletin./hatreachedaandco-expression)-,mul-tipleGWAShavebeenconductedinworldpopulationsMethodsandnumerousSZ-associatedvariantsandlociwereiden-22–35SNPAssociationsFromGWASof??icsistheestablishmentofPsychiatricGenomicsConsortium(PGC),whichper-SeveralGWASofSZhavebeenperformedduringtheformedthelargestGWASmeta-,identifiednumeroushigh-icriskvariantsPGC2performedthelargestmeta-,genome-,ancestry-matched,nonoverlappingcase-controlsamplesnovelriskvariantsandgenescannowbeidentifiedatand3family--analysiswas82315,including35476SZcasesandatUniversityofNottinghamonJuly26,2016inidentifyingSZriskvariants,understandingthepatho--,mostoftheSZ-associatedvariantsidenti-tion,associationtestwasperformedseparatelyineachfiedbyGWASresideinnoncodingregions(binedandmeta-ana-annotationandnoobviousfunctionalconsequence),-howtheseriskvariantscontributetoSZriskislargelytion,--tionofSZriskvariantsandtheextractionofmeaning-tics(SNPassociations),mon().Intotal,summarystatisticsicvariants(singlenucleotidepolymorphisms,SNPs),icvariationsincludingrarevariants,V),PlottingofRegionalAssociation?SignalandstructuralgenomicvariationsplayapivotalroleinTovisualizetheresultsofgenome-–41Therefore,thereisapressingneedtointegrate3645ofPGC2,-,sys-loadedfromthePGCwebsite(/tematicintegrationandin-depthanalysisofmulti-typepgc/downloads).36WedownloadedtheHg19genomedatafromvarioussources(eg,icandgeneexpres-assemblyand1000Genomespopulationdatafromhttp://sionstudies)/.,selectinghigh-confidencecandidategeneforfurtherfunctionalSNPFunctionAnnotationvalidationischallengingduetoalargenumberofgenesMostoftheSZ--lieinnoncodingregionandarepredominatelylocatedzationanalysis(eg,convergentfunctionalgenomics)42withinputativeregulatoryelements,36suggestingthatprovidesavaluablesolutionforselectingthecandidatethesevariantsmayconferrisktoSZthroughaffectingPage2of13:..SZDB:A?)developedbyJiaet??binedoddsratio(COR)method,?al56rankedinhumangenomeusingexperimentaldatasetsfromandprioritized38core(supplementarytableS4),48Briefly,high-through-SZcandidategenes(supplementarytableS5)andtheseputationalandexperimentaldatasets,-DNasefootprinting,bindingmotif,ChIP-seq,chromatinloadedandintegratedalltheseSZcandidategenesintostate,eQTL,aswellasothersourceswereusedtopredictSZDB,(supplementarytableS6),ascoresystemwas(2)(RegulomeDB,22–-/)wasdevelopedbyBoyleand46allyextractedSZriskgenesthatreachedthegenome-,375nonoverlappingDownloadedfromincreasingevidenceforavarianttobelocatedinafunc-genes(supplementarytableS7)(3)(CFG).ByusingaconvergentfunctionalgenomicsscoredataforallSNPs(includinggenotypedand4236approach,Ayalewet?alprioritized42promisingSZhttp://schizophreniabulletin./imputed)analyzedinPGC2andintegratedthesescorescandidategenes(supplementarytableS8)-synonymous(missense)vari-49,5051(4)-2,-synonymous(missense)?Genesgenes(supplementarytableS9)andintegratedthemPreviousstudies(iclinkageandasso-,18,19GWAS,36integrativestudiessuchas(5)(CFG)42andSherlockMultiplelinesofevidencesupporttheimportantroleintegrativeanalysis,52andwholeexomesequencingstud-,ies53,54)?al58developedastatisticalframework(namedatUniversityofNottinghamonJuly26,2016prehensiveSherlock)toidentifydisease-,SZcandidategeneswereclassifiedintotheWeperformedintegrativeanalysisusingSherlockandfollowingcategories:-gratedthese12genesintoSZDB.(1)iclinkageandassociation(6)-,Lewiset?alconductedaTodetectgenesthataredifferentiallyexpressedbetweenrank-basedgenomescanmeta-analysisandidentifiedSZpatientsandhealthycontrols,manylarge--,160genesloaded5microarraydatasets(whichusedbraintissueslocatedinthesechromosomalregionswereextracted19fromSZpatientsandcontrols)fromthegeneexpression(supplementarytableS1).Recently,Nget?alalsoper-omnibus(GEO;[.gov/geo/]),formedasystemati