Metabolite, immunocyte phenotype, and lymphoma: a Mendelian randomization study

作者：Chenyang Fan, Pengying Yuan, Xiangdong Yang, Weifeng Zhang, Xingli Wang, Juan Xie, Jing He, Haijing Chen, Lixiang Yan, Zhexin Shi · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1431261 · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Ferroptosis and cancer prognosis、Metabolomics and Mass Spectrometry Studies

Background: Recent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear. Objective: To elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis. Methods: Applying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype. Results: This study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma. In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a media...