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探讨血液代谢物与端粒长度之间的关联:一项孟德尔随机化研究。

Investigating the association between blood metabolites and telomere length: A mendelian randomization study.

机构信息

Head and Neck Surgeons, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fujian, China.

出版信息

PLoS One. 2024 Mar 8;19(3):e0298172. doi: 10.1371/journal.pone.0298172. eCollection 2024.

Abstract

BACKGROUND

Telomere length refers to the protective cap at the end of chromosomes, and it plays a crucial role in many diseases. The objective of this study is to explore the relationship between blood metabolites and telomere length, aiming to identify novel biological factors that influence telomere length.

METHODS

In this study, we extracted genome-wide association study (GWAS) data for blood metabolites from a sample of 7824 Europeans. Additionally, GWAS data for telomere length were obtained from the Open GWAS database (GWAS ID: ieu-b-4879). The primary analysis of this study utilized the random inverse variance weighted (IVW) method. Complementary analyses were also conducted using the MR-Egger and weighted median approaches. Sensitivity analyses were performed to assess the robustness of the findings. These included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. To investigate the possibility of reverse causation, reverse MR analysis was conducted. Additionally, multivariable MR was utilized to evaluate the direct effect of metabolites on telomere length.

RESULTS

The results suggested a potential association between 15-methylpalmitate, taurocholate, levulinate, and X-12712 and telomere length. MVMR analysis further showed that 15-methylpalmitate, taurocholate, and levulinate can directly influence telomere length, regardless of other metabolites.

CONCLUSIONS

This study suggests that 15-methylpalmitate, taurocholate, and levulinate are likely factors correlated with telomere length. These findings will contribute to the development of strategies for protecting telomeres, preventing related diseases, and establishing a new biological foundation for achieving healthy aging.

摘要

背景

端粒长度指的是染色体末端的保护帽,它在许多疾病中起着至关重要的作用。本研究旨在探讨血液代谢物与端粒长度之间的关系,旨在确定影响端粒长度的新的生物学因素。

方法

本研究从 7824 名欧洲人样本中提取了血液代谢物的全基因组关联研究(GWAS)数据。此外,还从 Open GWAS 数据库(GWAS ID:ieu-b-4879)获得了端粒长度的 GWAS 数据。本研究的主要分析采用了随机逆方差加权(IVW)方法。还使用了 MR-Egger 和加权中位数方法进行了补充分析。进行敏感性分析以评估研究结果的稳健性。这些分析包括 Cochran Q 检验、MR-Egger 截距检验、MR-PRESSO 和逐一排除分析。为了研究反向因果关系的可能性,进行了反向 MR 分析。此外,还使用多变量 MR 评估了代谢物对端粒长度的直接影响。

结果

研究结果表明,15-甲基棕榈酸酯、牛磺胆酸盐、戊二酸和 X-12712 与端粒长度之间存在潜在关联。MVMR 分析进一步表明,15-甲基棕榈酸酯、牛磺胆酸盐和戊二酸可以直接影响端粒长度,而与其他代谢物无关。

结论

本研究表明,15-甲基棕榈酸酯、牛磺胆酸盐和戊二酸可能是与端粒长度相关的因素。这些发现将有助于制定保护端粒、预防相关疾病的策略,并为实现健康老龄化建立新的生物学基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d34/10923442/a97feb90ace2/pone.0298172.g001.jpg

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