Chen Dongliang, Liu Shengchen, Li Jian, Zhou Yueyun, Jing Tong, Maimaiti Aizeretiaili, Huang Fuhua
Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Int J Cardiol Cardiovasc Risk Prev. 2025 May 13;26:200426. doi: 10.1016/j.ijcrp.2025.200426. eCollection 2025 Sep.
Previous studies have identified correlations between autoimmune and aortic diseases; however, the causal connection between these conditions remains uncertain and lack of comprehensiveness. This study aimed to investigate the potential causal relationships between autoimmune and aortic diseases from a genetic perspective.
A two-sample Mendelian randomization (MR) study was implemented to investigate the relationships between 17 common autoimmune diseases and aortic diseases. To serve as instrumental variables (IVs), we extracted single-nucleotide polymorphisms from both the genome-wide association study and the FinnGen databases. The inverse-variance weighted (IVW) approach was primarily employed to estimate causal links between autoimmune and aortic diseases. Several quality control assessments were conducted to maintain the rigor of the research, including heterogeneity tests, pleiotropy analyses, and sensitivity analyses.
Our MR study revealed a link between Addison's disease and an elevated risk of thoracic aortic aneurysm. In addition, Sjögren's syndrome and polymyalgia rheumatica showed negative and positive correlations with aortic dissection respectively. Although each of these two correlations was not statistically significant in the alternative sensitivity analysis, the estimates were in the same direction. No signs of horizontal heterogeneity or pleiotropy were detected in sensitivity analyses among these associations. The remaining 14 autoimmune diseases did not demonstrate a causal relationship with aortic diseases.
An increasing risk of thoracic aortic aneurysms may be related to Addison's disease. In addition, Sjögren's syndrome exhibited a negative association, while polymyalgia rheumatica exhibited a positive association with aortic dissection.
先前的研究已经确定了自身免疫性疾病与主动脉疾病之间的相关性;然而,这些病症之间的因果关系仍不明确且缺乏全面性。本研究旨在从遗传学角度探讨自身免疫性疾病与主动脉疾病之间潜在的因果关系。
开展了一项两样本孟德尔随机化(MR)研究,以调查17种常见自身免疫性疾病与主动脉疾病之间的关系。为了用作工具变量(IVs),我们从全基因组关联研究和芬兰基因数据库中提取了单核苷酸多态性。主要采用逆方差加权(IVW)方法来估计自身免疫性疾病与主动脉疾病之间的因果联系。进行了多项质量控制评估以保持研究的严谨性,包括异质性检验、多效性分析和敏感性分析。
我们的MR研究揭示了艾迪生病与胸主动脉瘤风险升高之间的联系。此外,干燥综合征和风湿性多肌痛分别与主动脉夹层呈负相关和正相关。尽管在替代敏感性分析中这两种相关性均无统计学意义,但估计值方向相同。在这些关联的敏感性分析中未检测到水平异质性或多效性的迹象。其余14种自身免疫性疾病与主动脉疾病未显示出因果关系。
胸主动脉瘤风险增加可能与艾迪生病有关。此外,干燥综合征与主动脉夹层呈负相关,而风湿性多肌痛与主动脉夹层呈正相关。