AB0006 ESTABLISHED RISK LOCI FOR SYSTEMIC LUPUS ERYTHEMATOSUS AT NCF2, STAT4, TNPO3, IRF5 AND ITGAM ASSOCIATE WITH DISTINCT CLINICAL MANIFESTATIONS: A DANISH GENOME-WIDE ASSOCIATION STUDY

Background Systemic lupus erythematosus (SLE) has been associated with more than 100 genetic loci. This parallels positively to the clinical diversity that is reflected by classification of SLE. Objectives We aimed investigate associations between disease manifestations SLE and risk gene variants relevant Danish subjects European ancestry. Methods included 427 patients ancestry similar previous reports.[1] also 89,699 controls from Blood Donor Study Genomic Cohort. loci in this population were identified genome-wide association methodology hereafter correlated cumulative occurrence items. Results Fourteen mapped following genes: NCF2, STAT4, TNPO3/TPI1P2, IRF5, ITGAM, significantly (p<5E-8) The five lead (p<0.05) manifestations; NCF2 : proteinuria anti-phospholipid antibodies, STAT4 arthritis, serositis, neurologic disorder, lymphopenia, anti-Smith antibodies , IRF5 seizures proteinuria, TNPO3 ITGAM photosensitivity (Table 2). Conclusion Our findings support future use select, markers predicting various phenotypes. References [1]Leffers HCB, Troldborg A, Voss et al. Smoking associates distinct phenotypes systemic erythematosus: a nationwide cross-sectional study. Lupus Sci Med 2021;8(1). Table 1. Associations specific SLE*. rs17849502_T rs7574865_T rs4728142_A rs13239597_A rs11860650_T N (%) Malar rash 233 (55%) 1.28 (0.84-1.96) 0.83 (0.62-1.11) 1.01 (0.74-1.38) 1.44 (0.97-2.12) 1.14 (0.80-1.61) Discoid 46 (11%) 1.49 (0.81-2.73) 0.90 (0.56-1.45) (0.62-1.66) 1.16 (0.63-2.12) 0.76 (0.42-1.41) Photosensitivity 219 (51%) 0.96 (0.63-1.46) 1.09 (0.81-1.47) 0.98 (0.71-1.34) 0.84 (0.57-1.25) 0.67 (0.47-0.97 ) Oral ulcers 132 (31%) (0.61-1.50) (0.65-1.23) (0.60-1.16) 1.30 (0.87-1.96) 1.43 (0.99-2.05) Non-erosive Arthritis 342 (80%) (0.52-1.37) (1.02-2.18 0.93 (0.63-1.36) 1.04 (0.64-1.68) (0.74-1.80) Serositis -Pleuritis 124 (29%) 0.63 (0.38-1.05) 1.38 (1.01-1.89 1.22 (0.87-1.72) 0.85 (0.56-1.29) (0.57-1.24) -Pericarditis 72 (17%) 0.75 (0.41-1.40) 1.35 (0.93-1.96) 1.05 (0.70-1.58) 1.15 (0.70-1.89) (0.70-1.72) Persistent 158 (37%) 1.63 (1.07-2.49 1.08 (0.80-1.46) 0.68 (0.49-0.94 1.74 (1.16-2.61 (0.76-1.57) Neurologic disorder -Seizures 23 (5%) 1.58 (0.75-3.35) (0.80-2.76) 2.10 (1.04-4.25 0.61 (0.26-1.44) (0.42-2.06) -Psychosis 8 (2%) (0.097-5.87) 2.77 (0.94-8.15) 0.35 (0.10-1.23) 0 (0) 2.96 (0.85-10.3) Haematologic -Haemolytic anaemia 38 (9%) 0.78 (0.34-1.76) 1.37 (0.85-2.22) (0.44-1.29) 1.11 (0.57-2.19) 1.24 (0.70-2.20) -Leukopenia 130 (30%) (0.67-1.61) 1.19 (0.87-1.63) 1.00 (0.72-1.39) (0.60-1.37) 0.94 (0.64-1.37) -Lymphopenia 228 (53%) 0.95 (0.63-1.44) (1.01-1.81 (0.70-1.29) (0.79-1.70) (0.77-1.54) -Thrombocytopenia 102 (24%) 1.42 (0.91-2.22) (0.60-1.18) (0.58-1.18) (0.86-2.11) 0.91 Immunologic -anti-DNA ab. 330 (77%) 0.69 (0.44-1.09) 1.02 (0.72-1.44) (0.65-1.35) 0.97 (0.62-1.53) (0.71-1.65) -anti-Smith 44 (10%) (0.79-2.64) (1.00-2.49 1.23 (0.73-2.07) 1.47 (0.80-2.69) 1.07 (0.61-1.84) -anti-phospholipid 183 (43%) (0.79-1.41) (0.61-1.14) (0.77-1.68) (0.80-1.62) * Logistic regression models for each manifestation all (multivariate) adjusted age sex Disclosure Interests Henrik Leffers: None declared, David Westergaard: Saedis Saevarsdottir: Ingileif Jonsdottir: Ole Birger Pedersen: Anne Troldborg: Voss: Salome Kristensen: Jesper Lindhardsen: Prabhat Kumar: Asta Linauskas: Lars Juul: Niels Steen Krogh: Bent Deleuran: Lene Dreyer Speakers bureau: Eli Lilly, Galderma Janssen, Grant/research from: BMS outside present work, Michael Schwinn: Lise wegner Thørner: Lotte Hindhede: Christian Erikstrup: Ullum: Søren Brunak Shareholder of: SB ownerships Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk Lundbeck Kari Stefansson: Karina Banasik: Jacobsen: declared