Xinlei Yang, Guojun Wei, Yu Fan, Han Gao, Shengxin Bao, Xiaobo Sun, Jiming Sun, Yiran Du
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引用次数: 0
摘要
目的：采用双样本孟德尔随机化（MR）方法探讨DNA甲基化加速（GAA）与脑肿瘤发病率之间的潜在因果关系。方法：我们利用公开的全基因组关联研究（GWAS）汇总数据，分析GAA（34,467名参与者）和脑肿瘤发病率（491,542名参与者）。26个单核苷酸多态性（SNPs）作为GAA的工具变量。方差反加权（IVW）是主要方法，MR-Egger、加权中位数、简单模式和加权模式是辅助方法。敏感性分析检验异质性和多效性。结果：IVW分析显示GAA与脑肿瘤风险无显著因果关系（β = -0.006, p = 0.908）。其他核磁共振方法也同意这一结论。敏感性检查，包括异质性和MR-Egger截距检验，支持这些无效发现。结论：我们的研究结果不支持GrimAge加速与脑肿瘤发病率之间的因果关系。GAA测量的加速表观遗传老化可能不是脑肿瘤风险的直接驱动因素。进一步的研究应探讨脑肿瘤病因中涉及的其他表观遗传或遗传因素。
Lack of a Causal Association between DNA Methylation GrimAge Acceleration and Brain Tumor Incidence: A Two-Sample Mendelian Randomization Study.
Objective: To investigate the potential causal relationship between DNA methylation GrimAge acceleration (GAA) and brain tumor incidence using a two-sample Mendelian randomization (MR) approach.
Methods: We leveraged publicly available genome-wide association study (GWAS) summary data for GAA (34,467 participants) and brain tumor incidence (491,542 participants). Twenty-six single nucleotide polymorphisms (SNPs) served as instrumental variables for GAA. Inverse variance weighted (IVW) was the primary method, complemented by MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses tested heterogeneity and pleiotropy.
Results: The IVW analysis indicated no significant causal effect of GAA on brain tumor risk (β = -0.006, p = 0.908). Other MR methods concurred. Sensitivity checks, including heterogeneity and MR-Egger intercept tests, supported these null findings.
Conclusion: Our results do not support a causal association between GrimAge acceleration and brain tumor incidence. Accelerated epigenetic aging, as measured by GAA, may not be a direct driver of brain tumor risk. Further investigations should explore other epigenetic or genetic factors implicated in brain tumor etiology.
期刊介绍：
The Journal of Multidisciplinary Healthcare (JMDH) aims to represent and publish research in healthcare areas delivered by practitioners of different disciplines. This includes studies and reviews conducted by multidisciplinary teams as well as research which evaluates or reports the results or conduct of such teams or healthcare processes in general. The journal covers a very wide range of areas and we welcome submissions from practitioners at all levels and from all over the world. Good healthcare is not bounded by person, place or time and the journal aims to reflect this. The JMDH is published as an open-access journal to allow this wide range of practical, patient relevant research to be immediately available to practitioners who can access and use it immediately upon publication.
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