遗传上预测了486种与食管癌风险有关的血液代谢物：孟德尔随机研究
Genetically predicted 486 blood metabolites in relation to risk of esophageal cancer: a Mendelian randomization study
影响因子:4.00000
分区:生物学3区 / 生化与分子生物学3区
发表日期:2024
作者:
Caiyan Jia, Dan Yi, Mingze Ma, Qian Xu, Yan Ou, Fanming Kong, Yingjie Jia
摘要
增强食管癌不同阶段的治疗选择并改善患者的生存，取决于及时且精确的诊断。血液代谢产物可能在引起或预防食管癌中发挥作用，但是需要进一步的研究来确定血液代谢物是否构成该疾病的遗传危险因素。为了解决这些问题，我们评估了食管癌与486种血液代谢产物之间的因果关系，这些血液代谢产物使用两样本的孟德尔随机分析（MR）研究起作用。为了暴露，我们使用了全基因组关联研究（GWAS）的486个代谢产物，以及Sakaue等人的食管癌的GWAS研究。用于初步分析。因果分析采用了随机逆差异加权（IVW）作为主要方法，并补充了MR-EGGER和加权中位数（WM）分析。敏感性分析包括MR-EGGER截距测试，Cochran Q检验，MR-Presso和剩余分析。另外，将独立的食管癌GWAS数据用于复制和荟萃分析。 FDR校正应用于识别因果关系的特征。为了确定的代谢物鉴定，我们进行了Steiger测试，连锁不平衡得分回归和共定位分析。 Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways.This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92，95％CI：1.17-3.17，p <0.01）和劳拉（Laurate）（12：0）（OR = 3.06，95％CI：1.38-6.78，p <0.01）。这项研究建立了三种定义的血统癌和食管癌症的因果关系，可将其具有新鲜的iNSIFTS。
Abstract
Enhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study.We utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways.This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17-3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38-6.78, p < 0.01).This study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.