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基因决定的端粒长度与脑膜瘤风险之间的因果关系。

The causal relationship between genetically determined telomere length and meningiomas risk.

作者信息

Yu Weijie, Mei Yunyun, Lu Zhenwei, Zhou Liwei, Jia Fang, Chen Sifang, Wang Zhanxiang

机构信息

The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.

Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, Xiamen Key Laboratory of Brain Center, Xiamen, China.

出版信息

Front Neurol. 2023 Aug 24;14:1178404. doi: 10.3389/fneur.2023.1178404. eCollection 2023.

Abstract

BACKGROUND

Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors.

METHODS

We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR).

RESULTS

In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14,  = 1.04 × 10], benign (OR = 4.81,  < 0.05), benign cerebral (OR = 5.36,  < 0.05), and benign unspecified meningioma (OR = 8.26,  < 0.05). The same results were obtained for the LTL-9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR = 4.94,  < 0.05), benign (OR = 3.14,  < 0.05), and benign cerebral meningioma (OR = 3.59,  < 0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR = 1.01,  < 0.05). No heterogeneity or horizontal pleiotropy was detected.

CONCLUSION

In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations.

摘要

背景

研究表明,白细胞端粒长度(LTL)较长与脑膜瘤风险增加显著相关。然而,关于LTL与良性和恶性脑膜瘤或良性肿瘤位置的因果关系的证据有限。

方法

我们使用了来自不同来源的三个LTL数据集,按名称和样本量分别命名为LTL - 78592、LTL - 9190和LTL - 472174。连锁不平衡评分(LDSC)用于探索LTL与脑膜瘤之间的关联。我们利用两样本双向孟德尔随机化(TSMR)来评估LTL是否与脑膜瘤风险存在因果关系。我们通过进行多变量孟德尔随机化(MVMR)来调整混杂因素。

结果

在LTL - 78592中,较长的LTL与恶性脑膜瘤风险增加显著相关[比值比(OR)= 5.14, = 1.04×10]、良性脑膜瘤(OR = 4.81, < 0.05)、大脑良性脑膜瘤(OR = 5.36, < 0.05)和未明确部位的良性脑膜瘤(OR = 8.26, < 0.05)。LTL - 9190也得到了相同的结果。在LTL - 472174中,较长的LTL与恶性脑膜瘤风险增加显著相关(OR = 4.94, < 0.05)、良性脑膜瘤(OR = 3.14, < 0.05)和大脑良性脑膜瘤(OR = 3.59, < 0.05)。MVMR也得到了类似结果。相比之下,只有大脑良性脑膜瘤显示出与较长LTL可能存在关联(OR = 1.01, < 0.05)。未检测到异质性或水平多效性。

结论

简而言之,在欧洲人群中,无论LTL测量方法如何,基因预测的较长LTL可能会增加良性、恶性和大脑良性脑膜瘤的风险。

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