Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

作者：Mengmeng Xiang, Yilun Wang, Zhanyan Gao, Jie Wang, Qian Chen, Zhan Sun, Jun Liang, Jinhua Xu · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2022.985729 · 被引用次数：116 · 研究领域：Systemic Lupus Erythematosus Research、Genetic Associations and Epidemiology、Diabetes and associated disorders

Objectives Previous studies have reported that a few inflammatory cytokines have associations with systemic lupus erythematosus (SLE)—for example, IL-6, IL-17, and macrophage inflammatory protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 inflammatory cytokines and SLE. Methods The two-sample Mendelian randomization utilized genetic variances of SLE from a large publicly available genome-wide association study (GWAS) (7,219 cases and 15,991 controls of European ancestry) and inflammatory cytokines from a GWAS summary containing 8,293 healthy participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were simultaneously applied to strengthen the final results. Results The results indicated that cutaneous T cell-attracting chemokine (CTACK) and IL-17 may be suggestively associated with the risk of SLE (odds ratio, OR: 1.21, 95%CI: 1.04–1.41, p = 0.015; OR: 1.37, 95%CI: 1.03–1.82, p = 0.029). In addition, cytokines including beta nerve growth factor, basic fibroblast growth factor, IL-4, IL-6, interferon gamma-induced protein 10, monokine induced by interferon-gamma, MIP1b, stromal cell-derived factor-1 alpha, and tumor necrosis factor-alpha are suggested to be the consequences of SLE disease (Beta: 0.035, p = 0.014; Beta: 0.021, p = 0.032; Beta: ...