■在自身免疫性疾病(AD)的背景下,颅内动脉瘤(IA)的发病机理尚不清楚。然而,AD的潜在全身性炎症特征可能通过共有的炎症途径影响IAs.因此,本研究旨在探讨ADs与IAs之间的关系并评估因果效应.
■在这项研究中,纳入6种常见AD,探讨其与IAs的因果关系。此外,我们进行了双向双样本单变量孟德尔随机化(UVMR)分析.此外,主要分析采用逆方差加权(IVW)和贝叶斯加权孟德尔随机化(BWMR)方法,并进行了一系列敏感性分析以评估结果的稳健性.Further,与AD和IA相关的数据来自开放全基因组关联研究(GWASs)和脑血管疾病知识门户(CDKP)(包括11,084例病例和311,458例对照),分别。这些分析是基于东亚和欧洲人群进行的。此外,6个ADs按结缔组织病分组,炎症性肠病,甲状腺疾病。在这个基础上,进一步进行多变量MR(MVMR1)分析,以探索每个AD和IAs之间的独立因果关系,并进行了MVMR2分析,以调查潜在的混杂因素,如吸烟,酒精消费,还有收缩压.最后,这些结果基于来自另一个IAs的GWAS数据进行了验证.
■UVMR分析结果表明,系统性红斑狼疮(SLE)与东亚人群中IAs的高风险相关(IVWOR,1.06;95CI,1.02-1.11;p=0.0065,UVMR),这得到了BWMR(OR,1.06;95CI,1.02-1.11;p=0.0067,BWMR),MVMR1(或,1.06;95CI,1.01-1.10;p=0.015,MVMR1),MVMR2(或,1.05;95CI,1.00-1.11;p=0.049,MVMR2),和敏感性分析。验证组的结果还表明SLE与IAs之间存在因果关系(IVWOR,1.04;95%CI,1.00-1.09;p=0.046)。反向MR分析结果未揭示IAs和AD之间的因果关系。
■在这项MR研究中,SLE被证实是东亚人群IAs的危险因素。因此,应强调SLE患者IAs的管理,以避免卒中事件.
UNASSIGNED: It remains unclear about the pathogenesis of intracranial aneurysms (IAs) in the setting of autoimmune disorders (ADs). However, the underlying systemic inflammatory characteristics of ADs may affect IAs through shared inflammatory pathways. Therefore, this study was conducted to explore the relationship between ADs and IAs and assess causal effects.
UNASSIGNED: In this study, 6 common ADs were included to explore their causal relationship with IAs. Besides, a bidirectional two-sample univariable Mendelian randomization (UVMR) analysis was performed. In addition, the primary analysis was performed by the inverse variance weighted (IVW) and Bayesian weighted Mendelian randomization (BWMR) method, and a series of sensitivity analyses were performed to assess the robustness of the results. Further, the data related to ADs and IAs were collected from open genome-wide association study studies (GWASs) and the Cerebrovascular Disease Knowledge Portal (CDKP) (including 11,084 cases and 311,458 controls), respectively. These analyses were conducted based on both the East Asian and European populations. Moreover, 6 ADs were subject to grouping according to connective tissue disease, inflammatory bowel disease, and thyroid disease. On that basis, a multivariate MR (MVMR1) analysis was further performed to explore the independent causal relationship between each AD and IAs, and an MVMR 2 analysis was conducted to investigate such potential confounders as smoking, alcohol consumption, and systolic blood pressure. Finally, these results were verified based on the data from another GWAS of IAs.
UNASSIGNED: The UVMR analysis results demonstrated that systemic lupus erythematosus (SLE) was associated with a high risk of IAs in the East Asian population (IVW OR, 1.06; 95%CI, 1.02-1.11; p = 0.0065, UVMR), which was supported by the results of BWMR (OR, 1.06; 95%CI, 1.02-1.11; p = 0.0067, BWMR), MVMR1 (OR, 1.06; 95%CI, 1.01-1.10; p = 0.015, MVMR1), MVMR2 (OR, 1.05; 95%CI, 1.00-1.11; p = 0.049, MVMR2), and sensitivity analyses. The results in the validation group also suggested a causal relationship between SLE and IAs (IVW OR, 1.04; 95% CI, 1.00-1.09; p = 0.046). The reverse MR analysis results did not reveal a causal relationship between IAs and ADs.
UNASSIGNED: In this MR study, SLE was validated to be a risk factor for IAs in the East Asian population. Therefore, the management of IAs in patients with SLE should be highlighted to avoid stroke events.