biostudies-literaturePatel ZHDepartment of Veteran Affairs and DefenseArthritis Foundation, Alliance for Lupus Research “Target Identification in Lupus”Ministry for Health and WelfareKey Research Program of the Chinese Academy of SciencesNCATS NIH HHSSpaulding Paolozzi Autoimmunity Center of ExcellenceProgram of the Shanghai Commission of Science and TechnologyNational Institutes of HealthState Key Laboratory of Oncogenes and Related GenesLupus Research Alliance “Novel Approaches” AwardNINDS NIH HHSNIAMS NIH HHSKirkland Scholar Award, National Basic ResearchSmartState Center of Economic Excellence in Inflammation and FibrosisProyecto de Excelencia of the Junta de AndalucíaRepublic of KoreaBLRD VANCRR NIH HHSNIAID NIH HHSNational Natural Science Foundation of ChinaNIHRichard M Silver MD Endowment for Inflammation ResearchNIDDK NIH HHSKorea Healthcare technology R&D ProjectNIMHD NIH HHSNHGRI NIH HHSCincinnati Children’s Research Foundation Endowed Scholar AwardNIGMS NIH HHS2392-2404https://www.ebi.ac.uk/biostudies/studies/S-EPMC6005081biostudies-literatureUnknown27(13)Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased Human molecular geneticsA plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.PMC600508112431900703UL1 TR000077R01AR057172I01 BX001834R01AR064820UL1 TR002535R01 AR063124P30 AR070549R21HG008186P60AR064464S10 RR027015–01P30 AR053483R01AR043727S10RR027015UL1TR001417P30 GM110766R21 AI070304R01AI082714P30 AR072579UL1 TR000004HG008666R01AR043274P30AR070549P30GM11076691-14-05R01AR44804R01 AI024717T32 GM063483P30 AR070155U54 GM104938UL1 TR001422R01AR069572R01 AR043814P30GM103510BX001834CTS2548U19 AI082714N01 AR0622774T32GM063483MD007909R01AR060366R01 AR072212R01AI024717P30 AR073750R01 AR069572U01 HG006828R21 AR06562681230072P60 AR053308K24AI078004R01 AI063274UL1TR000004P30 GM103510UL1RR029882R01AR063124R01 AR0603661U54TR001353R01 AR051545U54GM104938R01AR62277R01AR043814P01 AR049084P30AR053483P30AR055385T32 GM1055262014CB541901R01 MD007909UL1 TR000150UL1 TR000154P60AR062755P60 AR062755R21AI070304R01AI063274K24 AI078004HG006828P20 GM103456U01 HG008666R01 NS0990685T32GM105526TR000077R01AR051545U01AI101934UL1 RR029882R21 HG008186GM104938R01DK107502U01 AI130830ULTR000062R01 AR06482012JC1406000UL1 TR0014172U54MD007587R01 AR043274U19AI082714U01HG008666U01 AI101934P01AR49084UL1TR000154PR094002P60AR053308GM103456P60AR066464UL1TR000150P30 AR072582HI13C2124R01AR058959R01 AR057172U01AI130830R01 AR043727R01 AR056360K24AR02318R01AR065626K24AR002138R01 DK10750281421001P60 AR064464P01 AI083194R01AI083194U54 MD007587K24 AR002138KJZD-EW-L01-3R01AR056360S10 RR027015RC2 AR058959R01NS099068U01HG006828Glenn SBPujato MLu XMarion MCWallace DJShen NWeirauch MTReveille JDKaufman KMTsao BPAinsworth HCMartin JComeau MEChen XAlarcon GSZoller EEJames JACriswell LARamsey-Goldman RPons-Estel BAFreedman BIMerrill JTAdler AMaddox ANath SKBang SYLangefeld CDLynch AVila LMMagnusen AFSilverman EDScofield RHPetri MLee JWilliams AHZiegler JTGuthridge JMKimberly RPNiewold TBForney CRGaffney PMAlarcon-Riquelme MEAnaya JMLee HSHenrickson MGilkeson GSVyse TJBrunner HIBrown EEWakeland EKMiller DHuggins JLHarley JBSchroeder CNamjou BRaj PEdberg JCJacob COParks LPatel ZHSivils KLBae SCStevens AMBoackle SACunninghame Graham DKelly JAKottyan LCKamen DLWeisman MHfalseA plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased 2018-01-01T00:00:00Z2018 Jul2026-05-04T20:46:45.094Z2019-07-24T07:21:22ZS-EPMC60050812991239310.1093/hmg/ddy140