Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-06-03 DOI:10.1186/s40246-024-00622-8

Xinrui Wu, Cong Hu, Tianyang Wu, Xinxing Du, Zehong Peng, Wei Xue, Yonghui Chen, Liang Dong

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Abstract

Background: Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC).

Methods: Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls).

Results: Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer's disease, liver iron content, sex hormone binding global levels, naive CD4-CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs.

Conclusion: This study provides potential intervention measures for preventing LTL-induced PCs.

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基于欧洲血统的孟德尔随机证据，证明白细胞端粒长度对前列腺癌的因果效应。

背景：多项证据表明，白细胞端粒长度（LTL）会影响前列腺癌（PC）的发病：方法：在此，我们采用单核苷多态性（SNPs）作为LTL（n = 472 174）的工具变量（IVs），并进行孟德尔随机分析，以估计它们对PC（79 148例患者/61 106例对照和6311例患者/88 902例对照）的因果影响：结果：LTL每延长1个s.d，PCs的风险就会增加34%。此外，通过两步孟德尔随机法分析LTL与多发性硬化症之间的候选介导因素发现，在23个候选介导因素中，阿尔茨海默病、肝脏铁含量、性激素结合全局水平、幼稚CD4-CD8-T细胞% T细胞和循环瘦素水平发挥了重要的介导作用。没有强有力的证据支持LTL与所选的PCs介导因子之间存在反向因果关系。对前四种介导因素进行调整，而不是对循环瘦素水平进行调整，会降低LTL对PCs的影响：本研究为预防LTL诱发的多发性硬化症提供了潜在的干预措施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.