Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2024-08-27 DOI:10.1186/s13148-024-01728-5

Xin Zhuang, Peng Chen, Rong Yang, Xiaoying Man, Ruochen Wang, Yifen Shi

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引用次数: 0

Abstract

Background: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks.

Methods: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR).

Results: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, P_IVW = 0.034), MCH (OR = 0.801, P_IVW = 2.046e-06), MCV (OR = 0.801, P_IVW = 0.001), and MCHC (OR = 0.813, P_IVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, P_IVW = 0.007).

Conclusion: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.

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孟德尔随机分析揭示了血液癌症中表观遗传学和端粒生物学的综合效应。

背景：端粒缩短和表观遗传修饰是导致衰老和血液病的关键因素。本研究通过表观遗传时钟，探讨端粒长度和表观遗传年龄加速（EAA）与血液癌症、血细胞和生化标志物的关系：本研究主要利用欧洲后裔人群的全基因组关联研究作为工具变量，通过双向双样本孟德尔随机化（MR）方法探索暴露与结果之间的因果关系。MR 技术包括反方差加权 (IVW)、MR Egger 和加权中值模式。使用科克伦 Q 检验和 MR Egger 截距评估 MR 中的异质性和多义性，并通过多变量 MR（MVMR）进一步验证结论的稳健性：我们的研究表明，端粒长度越长，罹患多发性骨髓瘤、白血病和淋巴瘤（OR > 1，P IVW = 0.034）、MCH（OR = 0.801，PIVW = 2.046e-06）、MCV（OR = 0.801，PIVW = 0.001）和 MCHC（OR = 0.813，PIVW = 0.002）的风险就越高。此外，MVMR 分析显示 DNA 甲基化 PhenoAge 加速与碱性磷酸酶之间存在关联（OR = 1.026，PIVW = 0.007）：该研究阐明了端粒长度、EAA和血液恶性肿瘤之间的关系，进一步强调了端粒长度和EAA对预后的重要意义。这加深了我们对血液病发病机制的理解，为风险评估和治疗策略提供了参考。

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

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.