观察性研究表明多种炎症因子与吸烟和饮酒之间存在关联，但在流行病学调查中确定因果关系具有挑战性。我们采用了从全基因组关联研究 (GWAS) 中获得的 41 种细胞因子循环水平的遗传关联数据，该研究包含 8293 名芬兰参与者。 5 种物质使用表型的遗传数据是从包含 120 万欧洲受试者的 GWAS 数据集中获得的。然后，我们进行了双向孟德尔随机化（MR）研究。前瞻性结果表明，戒烟与肝细胞生长因子（HGF）、白介素-10（IL-10）和干细胞因子（SCF）呈正相关；每天吸烟是与基质细胞衍生因子 1α (SDF-1 A)、干扰素-γ (IFN-G)、IL-4 和粒细胞集落刺激因子 (G-CSF) 高表达相关的危险因素；每周饮酒和开始吸烟分别是与 HGF 和 IL-2RA 水平降低相关的危险因素。在反向 MR 分析中，结果显示 IL-16 和 IL-18 都会增加每天吸烟的风险；巨噬细胞炎症蛋白-1β（MIP-1B）和肿瘤坏死因子-β（TNF-B）分别抑制和促进戒烟；巨噬细胞集落刺激因子 (M-CSF) 会增加每周饮酒的风险，而干扰素诱导蛋白 10 (IP-10) 则具有相反的作用； IL-7和M-CSF分别延长和缩短开始经常吸烟的年龄。这项研究提供了支持各种炎症因子与成瘾表型之间因果关系的遗传证据。需要进一步全面的研究来揭示潜在的生物学机制。此外，文献计量研究表明，氧化应激是烟酒成瘾研究最重要的方向之一，深入研究其促炎机制将有助于开发潜在的治疗生物靶点和药物。© 2024 . Springer-Verlag GmbH 德国，隶属于 Springer Nature。

Observational studies have suggested associations between multiple inflammatory factors and tobacco and alcohol use, but establishing causation is challenging in epidemiological investigations. We employed genetic association data about the circulating levels of 41 cytokines obtained from the genome-wide association study (GWAS), which contained 8293 Finnish participants. Genetic data on 5 substance use phenotypes were obtained from the GWAS dataset containing 1.2 million European subjects. Then, we conducted a bidirectional mendelian randomization (MR) study. The forward results indicated that smoking cessation was positively correlated with hepatocyte growth factor (HGF), interleukin-10 (IL-10), and stem cell factor (SCF); cigarettes per day was a risk factor associated with high expression in stromal cell-derived factor 1α (SDF-1 A), interferon-γ (IFN-G), IL-4, and granulocyte colony-stimulating factor (G-CSF); drinks per week and smoking initiation were risk factors respectively correlated with reduced HGF and IL-2RA levels. During inverse MR analysis, the findings revealed that both IL-16 and IL-18 increased the risk of cigarettes per day; macrophage inflammatory protein-1β (MIP-1B) and tumor necrosis factor-β (TNF-B) inhibited and promoted smoking cessation, respectively; macrophage colony-stimulating factor (M-CSF) elevated the risk of drinks per week, while interferon inducible protein 10 (IP-10) had a contrary role; IL-7 and M-CSF respectively prolonged and shortened age of initiation of regular smoking. This study provides genetic proof supporting a causal relationship between various inflammatory factors and addiction phenotypes. Further comprehensive investigations are required to uncover underlying biological mechanisms. In addition, bibliometric studies have shown that oxidative stress is one of the most important orientations in alcohol and tobacco addiction research, where an in-depth investigation of its pro-inflammatory mechanisms would facilitate the development of potential therapeutic biological targets and drugs.© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.