端粒缩短和表观遗传修饰是衰老和血液疾病的关键因素。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、血细胞和生化标记物的关系。本研究主要利用欧洲血统人群的全基因组关联研究作为工具变量，探索通过双向双样本孟德尔随机化 (MR) 方法来确定暴露与结果之间的因果关系。 MR 技术包括逆方差加权 (IVW)、MR Egger 和加权中值模式。使用 Cochran's Q 检验和 MR Egger 截距评估 MR 的异质性和多效性，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，较长的端粒长度显着增加多发性骨髓瘤、白血病和癌症的风险。淋巴瘤（OR > 1，P < 0.05）并建立端粒长度与红细胞指数之间的因果关系，例如RBC（OR = 1.121，PIVW = 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）。此外，MVMR分析揭示了DNA甲基化PhenoAge加速与碱性磷酸酶之间的关联（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的预后意义。这加深了我们对血液疾病发病机制的理解，可以为风险评估和治疗策略提供信息。© 2024。作者。

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.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).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, PIVW = 0.034), MCH (OR = 0.801, PIVW = 2.046e-06), MCV (OR = 0.801, PIVW = 0.001), and MCHC (OR = 0.813, PIVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, PIVW = 0.007).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.© 2024. The Author(s).