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基于孟德尔随机化探讨免疫细胞与药物依赖的因果关系
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Abstract:
目的：采用两样本孟德尔随机化(MR)方法研究731种免疫细胞表型与药物依赖发病风险的因果效应。方法：在全基因组关联研究数据库(genome wide association study, GWAS)中筛选符合条件的731种免疫细胞表型及药物依赖的因果关系。共纳入了三种类型的免疫特征((MFI), RC, AC)。综合敏感性分析用于验证结果的异质性和水平多向性。结果：IVW结果显示免疫细胞与免疫细胞发病风险存在因果效应，其中两种免疫表型对药物依赖的保护作用：Activated Treg %CD4 Treg(OR = 0.859, 95%CI: 0.763~0.967, P = 0.012)、CD3 on activated Treg (OR = 0.881, 95%CI: 0.780~0.995, P = 0.042)。五种免疫表型对药物依赖的危害作用：CD28 on activated & secreting Treg (OR = 1.152, 95%CI: 1.006~1.320, P = 0.041)、CM DN (CD4-CD8-)%T cell (OR = 1.152, 95%CI: 1.017~1.305, P = 0.026)、HLA DR+ CD8br %lymphocyte (OR = 1.162, 95%CI: 1.032~1.308, P = 0.013)、Mo MDSC AC (OR = 1.135, 95%CI: 1.008~1.279, P = 0.037)、TD CD8br AC (OR = 1.398, 95%CI: 1.036~1.887, P = 0.028)。结论：我们的研究通过基因手段证明了免疫细胞与药物依赖之间的密切联系，从而为今后的临床研究与预防提供了指导。
Objective: A two-sample Mendelian randomisation (MR) approach was used to investigate the causal effect of 731 immune cell phenotypes on the risk of developing drug dependence. Methods: Eligible 731 immune cell phenotypes and drug-dependent causality were screened in the genome wide association study (GWAS) database. A total of three types of immune profiles (median fluorescence intensities (MFI), relative cell (RC), and absolute cell (AC)) were included. Comprehensive sensitivity analyses were used to validate the heterogeneity and horizontal multidirectionality of the results. Results IVW results showed a causal effect of immune cells and risk of immune cell pathogenesis, with two immune phenotypes protective against drug dependence: activated Treg %CD4 Treg (OR = 0.859, 95% CI: 0.763~0.967, P = 0.012), CD3 on activated Treg (OR = 0.881, 95% CI: 0.780~0.995, P = 0.042). Harmful effects of five immunophenotypes on drug dependence: CD28 on activated & secreting Treg (OR = 1.152, 95%CI: 1.006~1.320, P = 0.041), CM DN (CD4-CD8-)%T cell (OR = 1.152, 95%CI: 1.017~1.305, P = 0.026), HLA DR+ CD8br %lymphocyte (OR = 1.162, 95%CI: 1.032~1.308, P = 0.013), Mo MDSC AC (OR = 1.135, 95%CI: 1.008~1.279, P = 0.037), TD CD8br AC (OR = 1.398, 95%CI: 1.036~1.887, P = 0.028). Conclusions: Our study demonstrates a strong link between immune cells and drug dependence by genetic means, thus providing guidance for future clinical research and prevention.
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