Ab0105 causal association between il-7 levels and ankylosing spondylitis: a two-sample mendelian randomization study

Background Ankylosing spondylitis (AS) is an immune-mediated inflammatory arthritis that affects the axial skeleton. Currently, the cause of AS is still not known, so there is no way to prevent AS. Interleukin-7 (IL-7) is a restrictive and non repetitive cytokine, mainly produced by epithelial and stromal cells. The relationship between IL-7 and some inflammatory cytokines such as AS has been discussed in recent advances in the pathogenesis of AS, but a direct effect of IL-7 on AS has not been demonstrated [ 1 ] . Objectives Study to investigate the casual association between IL-7 and AS. Methods We evaluated the causal relationship between IL-7 levels and AS using a Mendelian randomization approach. The GWAS summary statistics of IL-7 (N = 3409) and AS (Ncase = 968, Ncontrol = 336,191) were downloaded from the IEU GWAS database in the study. Instrumental variables (IVs) were constructed using single nucleotide polymorphisms (SNPs). To assess the causal relation of IL-7 and AS, we used three analytical methods: MR-Egger mode, Weighted median mode, and Inverse variance weighted (IVW). In addition, we also conducted sensitivity tests, including the heterogeneity test, the pleiotropy test, the funnel plot, leave-one-out approach and MR-PRESSO. Results When selecting SNPs associated with IL-7, in the situation of the genome-wide significant threshold of P < 5×10-6 and LD r2 = 0.001, we finally obtained 9 IVs that could be used in the subsequent steps. Based on the IVW mode with high statistical power, a prudent and credible causal relationship was demonstrated between IL-7 and AS [IVW: P=0.025, OR(95%CI)=0.999(0.999, 1.000)]. As the level of IL-7 increased, the risk of developing AS also decreased, proving that IL-7 was a protective factor for this disease (Figure 1a). The Cochrane Q test (Q test p = 0.99) showed a good homogeneity among studies. The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any of the selected IVs (Figure 1b). Funnel plot results (Figure 1c) and the intercept of the MR-Egger regression (Figure 1d) further showed that pleiotropy did not bias the causal effect in this study. Conclusion Our research results show that IL-7 is causally associated with the pathogenesis of AS. which enables the early detection of AS, this findings have great clinical value. Reference [1]Pedersen SJ, Maksymowych WP. The Pathogenesis of Ankylosing Spondylitis: an Update. Curr Rheumatol Rep. 2019; 21 (10):58 ‘doi’: 10.1007/s11926-019-0856-3[‘2019-11-11]. Acknowledgements This work was supported by the Key R&D Program of Shanxi Province(201903D311011) and Taiyuan Science and Technology Plan (XG2020-5-06). Disclosure of Interests None Declared.