基于多变量孟德尔随机化的血清代谢物与肺癌的因果关联。
The causal association between serum metabolites and lung cancer based on multivariate Mendelian randomization.
机构信息
Department of Hematology and Oncology Laboratory, The Affiliated Shaoyang Hospital, Hengyang Medical School, University of South China.
Department of Scientific Research and Teaching, The Affiliated Shaoyang Hospital, Hengyang Medical School, University of South China.
出版信息
Medicine (Baltimore). 2024 Feb 16;103(7):e37085. doi: 10.1097/MD.0000000000037085.
This study seeks to understand the causal association between serum metabolites and different lung cancer types, an area yet to be extensively studied. We Used a two-sample Mendelian randomization (TSMR) approach, utilizing 486 blood metabolites as exposures and 3 distinct lung cancer types genome-wide association studies datasets as outcomes. We employed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode to estimate causal effects. We performed sensitivity analyses using Cochran Q test, MR-Egger intercept test, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Linkage disequilibrium score (LDSC) analysis was conducted on the selected metabolites, and common confounding single nucleotide polymorphisms were eliminated using the human genotype-phenotype association Database. Metabolic pathway analysis was performed with MetaboAnalyst 5.0 software. Subsequently, a multivariate Mendelian randomization analysis was conducted to ascertain independent risk exposures. Our findings suggest independent risk factors for specific types of lung cancer: 7-methylxanthine and isoleucine for lung adenocarcinoma, cysteine and 1-arachidonoylglycerophosphocholine are identified as independent protective and risk factors for squamous lung cancer. Undecanoate (11:0) with Linoleate (18:2n6) showed a protective effect for small cell lung cancer. Additionally, 11 metabolic pathways were associated with lung cancer. This novel perspective offers a multidimensional understanding of lung cancer phenotypes, providing valuable guidance for identifying and screening of diverse lung cancer phenotypes.
本研究旨在探讨血清代谢物与不同肺癌类型之间的因果关联,这是一个尚未得到广泛研究的领域。我们使用了两样本 Mendelian 随机化(TSMR)方法,将 486 种血液代谢物作为暴露因素,3 个不同的肺癌全基因组关联研究数据集作为结局。我们采用了逆方差加权、MR-Egger、加权中位数、简单模式和加权模式来估计因果效应。我们使用 Cochran Q 检验、MR-Egger 截距检验和 MR-Pleiotropy 残差和异常值(MR-PRESSO)进行了敏感性分析。我们对选定的代谢物进行了连锁不平衡评分(LDSC)分析,并使用人类基因型-表型关联数据库消除了常见的混杂单核苷酸多态性。我们使用 MetaboAnalyst 5.0 软件进行了代谢途径分析。随后,我们进行了多变量 Mendelian 随机化分析,以确定独立的风险暴露因素。我们的研究结果表明,特定类型的肺癌存在独立的风险因素:7-甲基黄嘌呤和异亮氨酸与肺腺癌有关,半胱氨酸和 1-花生四烯酰甘油磷酸胆碱被确定为鳞状肺癌的独立保护和风险因素。十一烷酸(11:0)与亚油酸(18:2n6)显示出对小细胞肺癌的保护作用。此外,有 11 条代谢途径与肺癌相关。这一新颖的视角提供了对肺癌表型的多维理解,为识别和筛选不同的肺癌表型提供了有价值的指导。