Risk and protective genetic variants in suicidal behaviour association with SLC1A2, SLC1A3, 5-HTR1B NTRK2 polymorphisms 英文参考文献.docVIP

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Risk and protective genetic variants in suicidal behaviour association with SLC1A2, SLC1A3, 5-HTR1B NTRK2 polymorphisms 英文参考文献.doc

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RiskandprotectivegeneticvariantsinsuicidalbehaviourassociationwithSLC1A2,SLC1A3,5-HTR1B

Murphyetal.BehavioralandBrainFunctions2011,7:22 /content/7/1/22 RESEARCH OpenAccess Riskandprotectivegeneticvariantsinsuicidal behaviour:associationwithSLC1A2,SLC1A3, 5-HTR1BNTRK2polymorphisms ThereseMMurphy1*,MariaRyan1,TomFoster2,ChrisKelly3,RoyMcClelland3,JohnO’Grady3,EleanorCorcoran4, JohnBrady4,MichaelReilly5,AnneJeffers6,KatherineBrown7,AnneMaher7,NoreenBannan8,AlisonCasement2, DermotLynch2,SharonBolger1,PrernaTewari9,AvrilBuckley10,LeahQuinlivan1,LeslieDaly11,12,CecilyKelleher12 andKevinMMalone1 Abstract Background:Suicidalbehaviourisknowntoaggregateinfamilies.Patientswithpsychiatricdisordersareathigher riskforsuicideattempts(SA),howeverprotectiveandriskgeneticvariantsforsuicideappeartobeindependentof underlyingpsychiatricdisorders.Hereweinvestigategeneticvariantsingenesimportantforneurobiological pathwayslinkedtosuicidalbehaviourand/orassociatedendophenotypes,forassociationwithSAamongpatients withco-existingpsychiatricillness.Selectedgene-geneandgene-environmentinteractionswerealsotested. Methods:DNAwasobtainedfrombloodsof159patients(76suicideattemptersand83non-attempters),who wereprofiledforDSM-IVAxisIpsychiatricdiagnosis.Twenty-eightsinglenucleotidepolymorphisms(SNPs)from18 candidategenes(COMT,5-HT2A,5-HT1A,5-HTR1B,TPH1,MAO-A,TPH2,DBH,CNR1,BDNF,ABCG1,GABRA5,GABRG2, GABRB2,SLC1A2,SLC1A3,NTRK2,CRHR1)weregenotyped.GenotypingwasperformedbyKBioscience.Testsof associationbetweengeneticvariantsandSAwereconductedusingChisquaredandArmitageTrendtests.Binary logisticalregressionanalyseswereperformedtoevaluatethecontributionofindividualgeneticvariantstothe predictionofSA,andtoexamineSNPsforpotentialgene-geneandgene-environmentinteractions. Results:Ouranalysisidentified4SNPs(rs4755404,rs2269272,rs6296andrs1659400),whichshowedevidenceof associationwithSAcomparedtoanon-attemptercontrolgroup.Weprovideevidenceofa3-locusgene-gene interaction,andaputativegene-environmentinteraction,wherebygeneticvariationattheNTRK2locusmay moderatetheriskassociatedwithhistoryofchildhoodabu