| 摘要: |
| 目的 采用孟德尔随机化(Mendelian randomization,MR)方法系统评估常见糖脂代谢性状与鼻咽癌(nasopharyngeal carcinoma,NPC)发病风险的因果关系,并在此基础上鉴定可能介导代谢性状影响NPC的血浆代谢物通路。方法 基于公开GWAS汇总数据,纳入6种代谢指标、1400项代谢表型,采用双样本MR及敏感性分析评估暴露与NPC风险关系,并用两步MR分析中介路径。结果 高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)与NPC风险呈提示性正向因果关联,其余5种未见显著关联。在1400项代谢表型筛查中,共64种代谢表型与NPC风险存在统计学关联(P<0.05),其中30种呈正向关联,34种呈负向关联。两步MR中介分析显示,鞘磷脂(sphingomyelin,SM)(d18:2/16:0,d18:1/16:1)和硫酸孕烯醇酮(pregnenolone sulfate,PregS)在HDL-C与NPC的关联路径中发挥保护性反向中介作用,中介比例分别为-42.13%和-18.00%。结论 HDL-C与NPC风险之间存在潜在遗传因果关联,两种血浆代谢物作为保护性中介参与该因果路径,可为NPC代谢机制研究及后续靶点探索提供参考。 |
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Chen Yang,Chen Qicong,Wang Gang,Li Min
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Guangxi University of Chinese Medicine
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| Abstract: |
| Objective: This study aimed to systematically evaluate the causal associations between common glycolipid metabolic traits and the risk of nasopharyngeal carcinoma (NPC) using Mendelian randomization (MR), and to further identify plasma metabolite pathways that may mediate the effects of metabolic traits on NPC. Methods: Publicly available genome-wide association study summary data were used. Six metabolic traits and 1,400 metabolic phenotypes were included. Two-sample MR analyses and sensitivity analyses were performed to assess the associations between exposures and NPC risk. Two-step MR was further applied to investigate potential mediation pathways. Results: High-density lipoprotein cholesterol (HDL-C) showed a suggestive positive causal association with NPC risk, whereas no significant associations were observed for the other five metabolic traits. Among the 1,400 metabolic phenotypes screened, 64 were statistically associated with NPC risk (P < 0.05), including 30 with positive associations and 34 with inverse associations. Two-step MR mediation analysis showed that sphingomyelin (SM) (d18:2/16:0, d18:1/16:1) and pregnenolone sulfate (PregS) acted as protective inverse mediators in the causal pathway from HDL-C to NPC, with mediation proportions of ?42.13% and ?18.00%, respectively. Conclusion: A potential genetic causal association was observed between HDL-C and NPC risk. Two plasma metabolites were identified as protective mediators in this causal pathway. These findings may provide insights into the metabolic mechanisms underlying NPC and inform future target exploration. |
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