Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis 英文参考文献.docVIP

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Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis 英文参考文献.doc

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Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis 英文参考文献

MultipleLociwithintheMajorHistocompatibility ComplexConferRiskofPsoriasis Bing-JianFeng1.,Liang-DanSun3,4.,RaziehSoltani-Arabshahi1,AnneM.Bowcock5,RajanP.Nair6, PhilipStuart6,JamesT.Elder6,StevenJ.Schrodi7,AnnB.Begovich7¤a,Gonc?alo R.Abecasis8 ,Xue-Jun Zhang2,3,4,KristinaP.Callis-Duffin1,GeraldG.Krueger1,DavidE.Goldgar1* 1DepartmentofDermatology,UniversityofUtahSchoolofMedicine,SaltLakeCity,UnitedStatesofAmerica,2InstituteofDermatology,AnhuiMedicalUniversity,Hefei, China,3DepartmentofDermatology,TheFirstAffiliatedHospitalofAnhuiMedicalUniversity,Hefei,China,4KeyLaboratoryofDermatology(AnhuiMedicalUniversity), MinistryofEducation,Hefei,China,5DepartmentofGenetics,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,6Departmentof Dermatology,UniversityofMichigan,AnnArbor,Michigan,UnitedStatesofAmerica,7Celera,Alameda,California,UnitedStatesofAmerica,8DepartmentofBiostatistics, UniversityofMichigan,AnnArbor,Michigan,UnitedStatesofAmerica Abstract Psoriasis is a common inflammatory skin disease characterized by thickened scaly red plaques. Previously we have performed a genome-wide association study (GWAS) on psoriasis with 1,359 cases and 1,400 controls, which were genotypedfor447,249SNPs.ThemostsignificantfindingwasforSNPrwhichisintightlinkagedisequilibrium withHLA-Cw*0602,theconsensusriskalleleforpsoriasis.However,itisnotknownwhetherthereareotherpsoriasisloci withintheMHCinadditiontoHLA-C.Inthepresentstudy,wesearchedforadditionalsusceptibilitylociwithinthehuman leukocyte antigen (HLA) region through in-depth analyses of the GWAS data; then, we followed up our findings in an independent Han Chinese 1,139 psoriasis cases and 1,132 controls. Using the phased CEPH dataset as a reference, we imputed the HLA-Cw*0602 in all samples with high accuracy. The association of the imputed HLA-Cw*0602 dosage with diseasewasmuchstrongerthanthatofthemostsignificantlyassociatedSNP,rAdjustingforHLA-Cw*0602 ,there weretworemainingassoc