孟德尔随机化探究细胞因子与深静脉血栓的因果效应

目的 深静脉血栓是一种受遗传和环境影响的复杂疾病。已有诸多研究证明免疫相关的细胞因子与深静脉血栓具有相关性，但尚无研究对它们之间的因果关系进行分析。因此，本研究利用孟德尔随机化模型系统地筛选对深静脉血栓有因果效应的细胞因子。方法 基于细胞因子和深静脉血栓的全基因组关联研究结果的数据，分别用IVW和MR-Egger两种两样本MR (Mendelian randomization)方法评估了包括生长因子、趋化因子、白介素、肿瘤坏死因子及其他类共计41个细胞因子与深静脉血栓和下肢深静脉血栓的因果关系，并利用多种方法检验多效性。结果 孟德尔随机化分析结果显示，白细胞介素12p70对深静脉血栓存在显著的正向因果效性(IVW: OR = 1.03; 95% CI: 1.01 ~ 1.04; P＜0.001)，对下肢深静脉血栓的发生也有潜在的促进作用(IVW: OR = 1.02; 95% CI: 1.01 ~ 1.04; P = 0.008)。结论 本研究结果表明白细胞介素12p70会促进深静脉血栓的形成。

Causal association between cytokines and deep vein thrombosis based on Mendelian randomization

Deep vein thrombosis(DVT) is a complex disease influenced by multiple genetic and environmental factors. Previous studies have shown that cytokines are correlated with deep vein thrombosis. However, the causal relationships between them have not been examined till now. Here we conduct Mendelian randomization(MR) analyses aiming to identify the cytokines which have causal effect on DVT. Methods We used both IVW and MR-Egger methods to assess the causality between 41 cytokines including growth factor, chemokines, interleukin, tumor necrosis factor, etc. and two phenotypes(DVT and DVT in leg) based on the data from genome-wide association studies on cytokines and DVT. Pleiotropy of final estimation was evaluated by multiple methods. Results MR analyses showed that interleukin-12 p70 increased the risk of DVT(IVW: OR=1.03; 95%CI: 1.01-1.04; P<0.001). For DVT in leg, the MR results revealed a significant causal effect of interleukin-12 p70(IVW: OR=1.02; 95%CI: 1.01-1.04; P=0.008). Conclusion The results suggest that interleukin12 p70 promotes the formation of DVT.