【摘要】 目的 采用两样本双向孟德尔随机化（MR）方法探究循环炎症因子与双相情感障碍之间潜在的因果关系。方法 从全基因组关联研究（GWAS）数据库中提取了包含14 824名参与者的91种循环炎症因子的遗传变异数据，从精神病基因组学联盟数据库的双相情感障碍工作组提取了41 917例双相情感障碍病例。以逆方差加权（IVW）为主要统计方法，通过IVW和MR-Egger进行Cochrane’s Q检验判定结果的异质性，通过MR-Egger截距检验进行结果的多效性检验，采用留一法检测结果的稳定性。结果 正向MR分析结果显示，肝细胞生长因子（HGF）的水平与双相情感障碍风险呈负相关；而肿瘤坏死因子（TNF）的水平与双相情感障碍的风险呈正相关。此外，在反向MR分析中，双相情感障碍的发生对白细胞介素-10(IL-10)的水平呈负相关关系。各项敏感性分析显示结果稳定，无明显异质性和多效性。结论 免疫功能紊乱与双相情感障碍之间存在复杂的相互作用关系。更多还原

【Abstract】 Objective To investigate the potential causal relationship between circulating inflammatory factors and bipolar disorder(BD) by using two-sample bidirectional Mendelian randomization(MR). Methods Two genetic instruments were obtained from the available public gene profile database. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study(GWAS) database of 14 824 participants. The bipolar disorder data, including 41 917 BD cases, were obtained from the bipolar disorder working group of the psychiatric genomics consortium database. Inverse variance weighted(IVW) was used as the main statistical method, and heterogeneity and pleiotropy tests were carried out through the Cochrane’s Q test and MR-Egger intercept test. Results The results of forward MR analysis revealed that the levels of hepatocyte growth factor(HGF) is inversely associated with the risk of BD; whereas the levels of tumor necrosis factor(TNF) are positively associated with the risk of BD. Additionally, in the reverse MR analysis interleukin-10(IL-10) were considered negative consequences of the occurrence of BD. Sensitivity analyses revealed no heterogeneity, pleiotropy and MR results are stable. Conclusion This study found the complex interaction between the immune dysfunction and BD.更多还原