Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimers Disease 英文参考文献.docVIP

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Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimers Disease 英文参考文献.doc

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Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimers Disease 英文参考文献

HippocampalAtrophyasaQuantitativeTraitina Genome-WideAssociationStudyIdentifyingNovel SusceptibilityGenesforAlzheimer’sDisease StevenG.Potkin1*,GuiaGuffanti1,2,AnitaLakatos1,JessicaA.Turner1,FrithjofKruggel3,JamesH. Fallon1,AndrewJ.Saykin4,AlessandroOrro5,SaraLupoli6,ErikaSalvi2,MichaelWeiner7 ,Fabio Macciardi1,2 fortheAlzheimer’sDiseaseNeuroimagingInitiative 1Department ofPsychiatryandHuman Behavior, UniversityofCaliforniaIrvine,Irvine, California, UnitedStates ofAmerica, 2Department ofSciencesandBiomedical Technologies,UniversityofMilan,Segrate(MI),Italy,3DepartmentofBiomedicalEngineering,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica, 4Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 5IstitutodiTecnologieBiomediche,ConsiglioNazionaledelleRicerche,Segrate(MI),Italy,6Universita’VitaeSalute,DepartmentofNeurologyandNeuroscience,Milan, Italy,7DepartmentofRadiology,PsychiatryandNeurology,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract Background:WiththeexceptionofAPOEe4allele,thecommongeneticriskfactorsforsporadicAlzheimer’sDisease(AD) areunknown. Methods and Findings: We completed a genome-wide association study on 381 participants in the ADNI (Alzheimer’s Disease Neuroimaging Initiative) study. Samples weregenotyped usingthe Illumina Human610-Quad BeadChip. 516,645 unique Single Nucleotide Polymorphisms (SNPs) were included in the analysis following quality control measures. The genotype dataand raw genetic dataare freely available for download (LONI, /ADNI/Data/). Two analyseswerecompleted:astandardcase-controlanalysis,andanovelapproachusinghippocampalatrophymeasuredon MRIasanobjectivelydefined,quantitativephenotype.AGeneralLinearModelwasappliedtoidentifySNPsforwhichthere wasaninteractionbetweenthegenotypeanddiagnosisonthequantitativetrait.Thecase-controlanalysisidentifiedAPOE and a new ris