Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population 英文参考文献.docVIP

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Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population 英文参考文献.doc

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Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population 英文参考文献

SequencingofDISC1PathwayGenesRevealsIncreased BurdenofRareMissenseVariantsinSchizophrenia PatientsfromaNorthernSwedishPopulation LotteN.Moens1,2,PeterDeRijk1,2,JokeReumers3,4,MaartenJ.A.VanDenBossche1,2,WimGlassee1,2 , SoniaDeZutter1,2,An-SofieLenaerts1,2,AnnelieNordin5,Lars-Go¨ranNilsson6,IgnacioMedinaCastello7, Karl-FredrikNorrback5,DirkGoossens1,2,KristelVanSteen8,RolfAdolfsson5,JurgenDel-Favero1,2* 1Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium, 2University of Antwerp (UA), Antwerp,Belgium,3SWITCHLaboratory,FlandersInstituteforBiotechnology(VIB),Flanders,Belgium,4VrijeUniversiteitBrussel(VUB),Brussels,Belgium,5Divisionof Psychiatry, Department of Clinical Sciences, Umea? University, Umea?, Sweden, 6Department of Psychology, Stockholm University, Stockholm, Sweden, 7Functional GenomicsUnit,BioinformaticsandGenomicsDepartment,PrinceFelipeResearchCentre(CIPF),Valencia,Spain,8SystemsandModelingUnit,MontefioreInstitute/GIGA, UniversityofLie`ge,Lie`ge,Belgium Abstract Inrecentyears,DISC1hasemergedasoneofthemostcredibleandbestsupportedcandidategenesforschizophreniaand relatedneuropsychiatricdisorders.Furthermore,increasingevidence–bothgeneticandfunctional–indicatesthatmanyof itsproteininteractionpartnersarealsoinvolvedinthedevelopmentofthesediseases.Inthisstudy,weappliedapooled sample454sequencingstrategy,toexplorethecontributionofgeneticvariationinDISC1and10ofitsinteractionpartners (ATF5,Grb2,FEZ1,LIS-1,PDE4B,NDE1,NDEL1,TRAF3IP1,YWHAE,andZNF365)toschizophreniasusceptibilityinanisolated northernSwedishpopulation.Mutationburdenanalysisoftheidentifiedvariantsinapopulationof486SZpatientsand514 control individuals, revealed that non-synonymous rare variants with a MAF,0.01 were significantly more present in patientscomparedtocontrols(8.64%versus4.7%,P=0.018),providingfurtherevidencefortheinvolvementofDISC1and some of its interaction partners in psychiatric disorders. This increased burden