Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, China.
Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, China.
BMC Cancer. 2024 Nov 21;24(1):1439. doi: 10.1186/s12885-024-13212-7.
The genetic causal association between the mitochondrial DNA copy number (mtDNA-CN) and the development of glioma and glioblastoma (GBM) remains unclear.
The summary-level datasets for mtDNA-CN were obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Additionally, summary statistics datasets related to glioma were collected from a comprehensive meta-analysis genome-wide association study, which included 12,488 cases and 18,169 controls. The main method employed was inverse variance weighting, supplemented by Bonferroni correction to account for multiple tests. Additionally, sensitivity analyses were performed to address potential pleiotropy and strengthen the reliability of the results.
In the primary analysis, no genetic causal association was found between mtDNA-CN and glioma (OR = 1.20, 95%CI = 0.94-1.52, P = 0.1394), nor with low-grade glioma (OR = 1.09, 95%CI = 0.79-1.51, P = 0.5588). However, a suggestive genetic relationship between mtDNA-CN and glioblastoma was observed (OR = 1.42, 95%CI = 1.02-1.96, P = 0.0347). These findings were replicated in the MR analysis. Comprehensive analyses, including heterogeneity and pleiotropy analyses, as well as reverse analysis, confirmed the robustness of these results.
Our MR study did not find a genetic causal association between mtDNA-CN and the risk of glioma. A suggestive causal association between GBM and mtDNA-CN was detected.
线粒体 DNA 拷贝数（mtDNA-CN）与神经胶质瘤和胶质母细胞瘤（GBM）发展之间的遗传因果关系仍不清楚。
从英国生物库和基因组流行病学中心与心脏和衰老研究队列的参与者中获得了 mtDNA-CN 的汇总数据集。此外，还从一项全基因组关联研究的综合荟萃分析中收集了与神经胶质瘤相关的汇总统计数据集，其中包括 12488 例病例和 18169 例对照。主要方法是逆方差加权，辅之以 Bonferroni 校正以考虑多重检验。此外，还进行了敏感性分析以解决潜在的多效性并增强结果的可靠性。
在主要分析中，mtDNA-CN 与神经胶质瘤（OR=1.20，95%CI=0.94-1.52，P=0.1394）或低级别神经胶质瘤（OR=1.09，95%CI=0.79-1.51，P=0.5588）之间未发现遗传因果关系。然而，mtDNA-CN 与胶质母细胞瘤之间存在提示性遗传关系（OR=1.42，95%CI=1.02-1.96，P=0.0347）。这些发现在 MR 分析中得到了复制。全面分析，包括异质性和多效性分析以及反向分析，证实了这些结果的稳健性。
我们的 MR 研究未发现 mtDNA-CN 与神经胶质瘤风险之间存在遗传因果关系。检测到 GBM 与 mtDNA-CN 之间存在提示性因果关系。
