Inflammation is associated with thoracic aortic aneurysm (TAA) but the effects of each circulating inflammatory factor on TAA remain unclear. In this study, we explored the relationship between circulating inflammatory factors and TAA risk using Mendelian randomization (MR) approach based on summary statistics from the latest genome-wide association study (GWAS) of 41 circulating inflammatory factors in 8293 Finns and a GWAS involving 1351 TAA cases and 18,295 controls of European ancestry. In univariable MR, higher interferon gamma-induced protein 10 (IP-10) levels, higher interferon gamma (IFNγ) levels and higher stem cell growth factor beta (SCGFβ) levels were associated with an increased risk of TAA (OR = 1.37, 95 % CI = 1.17–1.59, p = 7.42 × 10; OR = 1.43, 95 % CI = 1.19–1.74, p = 2.04 × 10; OR = 1.27, 95 % CI = 1.09–1.48, p = 2.40 × 10, respectively). In multivariable MR, the patterns of associations for the three cytokines remained adjusting for each other or smoking, but were attenuated differently with adjustment for other cardiovascular risk factors, especially for lipids and body mass index. Bidirectional MR approach did not identify any significant associations between cytokines and risk factors. Our results indicated that circulating cytokines may play mediation roles in the pathogenesis of TAA. Further studies are needed to determine whether these biomarkers can be used to prevent and treat TAA.

中文翻译：

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与胸主动脉瘤相关的循环 IP-10、IFNγ 和 SCGFβ 水平升高的遗传倾向：孟德尔随机研究

炎症与胸主动脉瘤 (TAA) 有关，但每种循环炎症因子对 TAA 的影响仍不清楚。在这项研究中，我们利用孟德尔随机化 (MR) 方法探讨了循环炎症因子与 TAA 风险之间的关系，该方法基于最新的全基因组关联研究 (GWAS) 的汇总统计数据，该研究涉及 8293 名芬兰人的 41 种循环炎症因子和涉及 1351 名芬兰人的 GWAS TAA 病例和 18,295 例欧洲血统对照。在单变量 MR 中，较高的干扰素 γ 诱导蛋白 10 (IP-10) 水平、较高的干扰素 γ (IFNγ) 水平和较高的干细胞生长因子 β (SCGFβ) 水平与 TAA 风险增加相关（OR = 1.37, 95 % CI = 1.17–1.59，p = 7.42 × 10；OR = 1.43，95 % CI = 1.19–1.74，p = 2.04 × 10；OR = 1.27，95 % CI = 1.09–1.48，p = 2.40 × 10 ）。在多变量 MR 中，三种细胞因子的关联模式仍然根据彼此或吸烟进行调整，但随着其他心血管危险因素（尤其是血脂和体重指数）的调整而不同程度地减弱。双向 MR 方法未发现细胞因子和危险因素之间存在任何显着关联。我们的结果表明循环细胞因子可能在 TAA 的发病机制中发挥介导作用。需要进一步的研究来确定这些生物标志物是否可以用于预防和治疗 TAA。