Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus 英文参考文献.docVIP

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Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus 英文参考文献.doc

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Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus 英文参考文献

AssociationofNCF2,IKZF1,IRF8,IFIH1,andTYK2with SystemicLupusErythematosus DeborahS.CunninghameGraham1,2,DavidL.Morris1,2,TusharR.Bhangale3,LindseyA.Criswell4 ,Ann- ChristineSyva¨nen5,LarsRo¨nnblom6,TimothyW.Behrens7,RobertR.Graham7,TimothyJ.Vyse1,2* 1DepartmentofMedicalandMolecularGenetics,DivisionofGeneticsandMolecularMedicine,SchoolofMedicine,King’sCollegeLondon,London,UnitedKingdom, 2AcademicDepartmentofRheumatology,DivisionofImmunology,Infection,andInflammatoryDiseases,SchoolofMedicine,King’sCollegeLondon,London,United Kingdom,3DepartmentofBioinformaticsandComputationalBiology,Genentech,SouthSanFrancisco,California,UnitedStatesofAmerica,4RosalindRussellMedical ResearchCenterforArthritis,DivisionofRheumatology,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,5MolecularMedicine, DepartmentofMedicalSciences,UppsalaUniversity,Uppsala,Sweden,6SectionofRheumatology,DepartmentofMedicalSciences,UppsalaUniversity,Uppsala,Sweden, 7ITGRHumanGeneticsGroup,Genentech,SanFrancisco,California,UnitedStatesofAmerica Abstract Systemiclupuserythematosus(SLE)isacomplextraitcharacterisedbytheproductionofarangeofauto-antibodiesanda diverse set of clinical phenotypes. Currently, ,8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR.1.3).InordertoidentifyadditionalgenescontributingtoSLEsusceptibility,weconductedareplicationstudyinaUK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis inthe UKdataset andsubsequent meta-analysis withthepublished data identifiedfive SLE susceptibility genes reaching genome-widelevelsof significance(Pcomb,561028): NCF2(Pcomb=2, IKZF1 (Pcomb=2.3361029), IRF8 (Pcomb=1.2461028),IFIH1(Pcomb=1.6361028),andTYK2(Pcomb=3.8861028).Eachofthefivenewlociidentifiedherecan bemappedintointerferonsignallingpath