AB0145 GENETIC EVIDENCE REVEALS A CAUSAL ROLE OF BLOOD LEUKOCYTE COUNTS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background Blood leukocyte counts are important biomarkers for the onset of systemic lupus erythematosus (SLE)[1-3]. However, causal relationship is unclear. Objectives We implement a two-sample Mendelian Randomization (MR) analysis to investigate potential association. Methods The summary statistics blood were available from public databases (n=172435)[4]. SNPs related SLE risk extracted large GWAS with 5201 cases and 9066 controls European ancestry[5]. All genetic variants significantly associated (p<5×10 -8 ) used as instrumental variables (IVs). Then, linkage disequilibrium (LD) was excluded (distance threshold = 10,000 kb, r 2 0.001). In this study, inverse variance weighted (IVW) method, MR-Egger median (WM) estimate effect SLE. addition, Cochran’s Q test, MR pleiotropy residual sum outlier (MR-PRESSO), leave-one-out implemented sensitivity tests. Results selected 119 independent IVs in total WBC. Higher lower (OR:0.629, 95% CI: 0.436-0.907, P: 0.013) by IVW method (Figure 1). results Cochrane showed heterogeneity (p<0.05). Therefore, we random-effects model[6]. Conclusion Our study predicted genetically that individuals face higher SLE, which consistent previous observational studies. References [1]Messner, R.P., F.D. Lindström, R.C. Williams, Jr., Peripheral lymphocyte cell surface markers during course erythematosus. J Clin Invest, 1973. 52 (12): p. 3046-56. [2]Nakano, M., et al., Increased Proportion CD226(+) B Cells Is Associated With Disease Activity Prognosis Systemic Lupus Erythematosus. Front Immunol, 2021. 12 : 713225. [3]Martínez-Baños, D., Moderate severe neutropenia patients Rheumatology (Oxford), 2006. 45 (8): 994-8. [4]Astle, W.J., Allelic Landscape Human Cell Trait Variation Links Common Complex Disease. Cell, 2016. 167 (5): 1415-1429.e19. [5]Bentham, J., Genetic association analyses implicate aberrant regulation innate adaptive immunity genes pathogenesis Nat Genet, 2015. 47 1457-1464. [6]DerSimonian, R. N. Laird, Meta-analysis clinical trials. Control Trials, 1986. 7 (3): 177-88. Figure 1: (A) Forest plot estimates on different methods. (B) Scatter plots analyses. (C) Funnel Acknowledgements: NIL. Disclosure Interests None Declared.