Persistence Criteria for Susceptibility Genes for Schizophrenia a Discussion from an Evolutionary Viewpoint 英文参考文献.docVIP

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Persistence Criteria for Susceptibility Genes for Schizophrenia a Discussion from an Evolutionary Viewpoint 英文参考文献.doc

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Persistence Criteria for Susceptibility Genes for Schizophrenia a Discussion from an Evolutionary Viewpoint 英文参考文献

PersistenceCriteriaforSusceptibilityGenesfor Schizophrenia:aDiscussionfromanEvolutionary Viewpoint NagafumiDoi1*,YokoHoshi2,MasanariItokawa3,ChieUsui4,TakeoYoshikawa5,HirokazuTachikawa1,6 1Department of Psychiatry, Ibaraki Prefectural Tomobe Hospital, Kasama-shi, Ibaraki, Japan, 2Integrated Neuroscience Research Team, Tokyo Institute of Psychiatry, Kamikitazawa, Setagaya-ku, Tokyo, Japan, 3Schizophrenia Research Project, Tokyo Institute of Psychiatry, Kamikitazawa, Setagaya-ku, Tokyo, Japan, 4Department of Psychiatry,FacultyofMedicine,JuntendoUniversity,Tokyo,Japan,5LaboratoryforMolecularPsychiatry,RIKENBrainScienceInstitute,Hirosawa,Wako,Saitama,Japan, 6DepartmentofPsychiatry,GraduateSchoolofComprehensiveHumanScience,TsukubaUniversity,Tsukuba,Ibaraki,Japan Abstract Background:Thecentralparadoxofschizophreniageneticsisthatsusceptibilitygenesarepreservedinthehumangene- poolagainstastrongnegativeselectionpressure.Substantialevidenceofepidemiologysuggeststhatnuclearsusceptibility genes,ifpresent,shouldbesustainedbymutation-selectionbalancewithoutheterozygoteadvantage.Therefore,putative nuclearsusceptibilitygenesforschizophreniashouldmeetspecialconditionsforthepersistenceofthediseaseaswellas theconditionofbearingapositiveassociationwiththedisease. Methodology/PrincipalFindings:Wededucedtwocriteriathateverynuclearsusceptibilitygeneforschizophreniashould fulfillforthepersistenceofthediseaseundergeneralassumptionsofthemultifactorialthresholdmodel.Thefirstcriterion demandsanupperlimitofthecase-controldifferenceoftheallelefrequencies,whichisdeterminedbythemutationrateat thelocus,andtheprevalenceandtheselectioncoefficientofthedisease.Thesecondcriteriondemandsanupperlimitof oddsratioforagivenallelefrequencyintheunaffectedpopulation.Whenweexaminedthetop30genesatSZGeneand the recently reported common variants on chromosome 6p with the criteria using the epidemiological data in a large- sampledFinnishcohortstudy,itwassuggestedthatmostoftheseareunlikelytoconfersusceptibilitytosc