Growing evidence suggests that inflammation is a significant contributor to different cardiovascular diseases (CVDs). Mendelian randomization (MR) was performed to assess the causal inference between plasma soluble IL6 receptor (sIL6R), a negative regulator of IL6 signaling, and different cardiovascular and immune-related disorders. Cis-MR with multiple instrumental variables showed an inverse association of sIL6R with rheumatoid arthritis, atrial fibrillation, stroke, coronary artery disease, and abdominal aortic aneurysm. However, genetically-determined sIL6R level was positively associated with atopic dermatitis and asthma. Also, sIL6R level was associated with longevity, as evaluated by parental age at death, a heritable trait. Gene-based association analysis with S-PrediXcan by using tissues from GTExV7 showed that IL6R tissue expression-disease pair associations were consistent with the directional effect of IL6 signaling identified in MR. Genetically-determined reduced IL6 signaling lowers the risk of multiple CVDs and is associated with increased longevity, but at the expense of higher atopic risk.

越来越多的证据表明炎症是不同心血管疾病 (CVD) 的重要诱因。孟德尔随机化 (MR) 旨在评估血浆可溶性 IL6 受体 (sIL6R)（IL6 信号传导的负调节因子）与不同心血管和免疫相关疾病之间的因果关系。具有多个仪器变量的Cis -MR 显示 sIL6R 与类风湿关节炎、心房颤动、中风、冠状动脉疾病和腹主动脉瘤呈负相关。然而，基因决定的 sIL6R 水平与特应性皮炎和哮喘呈正相关。此外，sIL6R 水平与长寿相关，根据父母死亡时的年龄（一种可遗传的特征）进行评估。使用 GTExV7 组织进行的 S-PrediXcan 基于基因的关联分析表明，IL6R组织表达-疾病对关联与 MR 中鉴定的 IL6 信号传导的方向性效应一致。基因决定的 IL6 信号传导减少可降低多种 CVD 的风险，并与寿命延长相关，但代价是更高的特应性风险。