Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function 英文参考文献.docVIP
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Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function 英文参考文献
AccuratelyAssessingtheRiskofSchizophrenia
ConferredbyRareCopy-NumberVariationAffecting
GeneswithBrainFunction
SoumyaRaychaudhuri1,2,3,JoshuaM.Korn1,2,4,StevenA.McCarroll1,5,TheInternationalSchizophrenia
Consortium,DavidAltshuler1,2,5,6,PamelaSklar7,8,9,ShaunPurcell8,9*,MarkJ.Daly1,2
*
1PrograminMedicalandPopulationGenetics,BroadInstitute,Cambridge,Massachusetts,UnitedStatesofAmerica,2CenterforHumanGeneticResearch,Massachusetts
General Hospital, Boston, Massachusetts, United States of America, 3Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston,
Massachusetts,UnitedStatesofAmerica,4GraduatePrograminBiophysics,HarvardUniversity,Cambridge,Massachusetts,UnitedStatesofAmerica,5Departmentof
Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 6Department of Molecular Biology, Massachusetts General Hospital, Boston,
Massachusetts,UnitedStatesofAmerica,7DepartmentofPsychiatry,MassachusettsGeneralHospital,Boston,Massachusetts,UnitedStatesofAmerica,8Psychiatricand
NeurodevelopmentalGeneticsUnit,MassachusettsGeneralHospital,Boston,Massachusetts,UnitedStatesofAmerica,9StanleyCenterforPsychiatricResearch,Broad
Institute,Cambridge,Massachusetts,UnitedStatesofAmerica
Abstract
Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One
hypothesisisthatCNVeventscausediseasebyaffectinggeneswithspecificbrainfunctions.Underthesecircumstances,we
expectthatCNVeventsincasesshouldimpactbrain-functiongenesmorefrequentlythanthoseeventsincontrols.Previous
publicationshaveapplied‘‘pathway’’analysestogeneswithinneuropsychiatriccaseCNVstoshowenrichmentforbrain-
functions.Whilesuchanalyseshavebeensuggestive,theyoftenhavenotrigorouslycomparedtheratesofCNVsimpacting
geneswithbrainfunctionincasestocontrols,andthereforedonotaddressimportantconfounderssuchasthelargesizeof
brain genes andoverall differences inrates andsizes of CNVs.To demonstrate thepotential impact of confounde
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