An Assessment of the Individual and Collective Effects of Variants on Height Using Twins and a Developmentally Informative Study Design 英文参考文献.docVIP

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An Assessment of the Individual and Collective Effects of Variants on Height Using Twins and a Developmentally Informative Study Design 英文参考文献.doc

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An Assessment of the Individual and Collective Effects of Variants on Height Using Twins and a Developmentally Informative Study Design 英文参考文献

AnAssessmentoftheIndividualandCollectiveEffectsof VariantsonHeightUsingTwinsandaDevelopmentally InformativeStudyDesign ScottI.Vrieze1,2*,MattMcGue1,MichaelB.Miller1,LisaN.Legrand1,NicholasJ.Schork3,WilliamG. Iacono1 1PsychologyDepartment,UniversityofMinnesota,Minneapolis,Minnesota,UnitedStatesofAmerica,2MinneapolisVAMedicalCenter,Minneapolis,Minnesota,United StatesofAmerica,3TheScrippsTranslationalScienceInstituteandtheScrippsResearchInstitute,LaJolla,California,UnitedStatesofAmerica Abstract Inasampleof3,187twinsand3,294oftheirparents,wesoughttoinvestigateassociationofbothindividualvariantsanda genotype-basedheightscoreinvolving176ofthe180commongeneticvariantswithadultheightidentifiedrecentlybythe GIANT consortium. First, longitudinal observations on height spanning pre-adolescence through adulthood in the twin sampleallowedustoinvestigatetheseparateeffectsofthepreviouslyidentifiedSNPsonpre-pubertalheightandpubertal growthspurt.WeshowthattheeffectofSNPsidentifiedbytheGIANTconsortiumisprimarilyonprepubertalheight.Only oneSNP,rs7759938inLIN28B,approachedasignificantassociationwithpubertalgrowth.Second,weshowhowusingthe twindatatocontrolstatisticallyforenvironmentalvariancecanprovideinsightintotheultimatemagnitudeofSNPeffects andconsequentlythegeneticarchitectureofaphenotype.Specifically,wecomputedageneticscorebyweightingSNPs accordingtotheireffectsasassessedviameta-analysis.Thisweightedscoreaccountedfor9.2%ofthephenotypicvariance in height, but 14.3% of the corresponding genetic variance. Longitudinal samples will be needed to understand the developmentalcontextofcommongeneticvariantsidentifiedthroughGWAS,whilegeneticallyinformativedesignswillbe helpful in accurately characterizing the extent to which these variants account for genetic, and not just phenotypic, variance. Citation:VriezeSI,McGueM,MillerMB,LegrandLN,SchorkNJ,etal.(2011)AnAssessmentoftheIndividualandCollectiveEffectsofVariantsonHeightUsing TwinsandaDevelopmentallyInformativeStudyDesign.PLoSGenet7(12):