Cao Shang-Mei, Luo Meng, Chen Bo-Lin, Fu Xiu-Hong
Department of Science and Technology Innovation Center, Luohe Central Hospital, The First Affiliated Hospital of Luohe Medical College, Henan Key Laboratory of Fertility Protection and Aristogenesis, Luohe, China.
School of Clinical Medicine, Henan University, Kaifeng, China.
Rejuvenation Res. 2025 Feb;28(1):1-8. doi: 10.1089/rej.2024.0039. Epub 2024 Sep 16.
Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (tA) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, = 0.012). The MR analysis indicated that metabolites (tA) may be causally associated with a positive effect on VD.
血管性痴呆(VD)的发病机制仍不清楚,目前尚无有效的预防和治疗方法。我们利用代谢物和VD的大规模全基因组关联研究(GWAS)的汇总统计数据应用孟德尔随机化(MR)来揭示代谢物对VD的因果效应。使用一组遗传工具进行分析,这些工具来自公开可用的遗传汇总数据。即32个与代谢物密切相关的单核苷酸多态性。采用逆方差加权法、加权中位数法、MR-Egger回归法和MR多效性残差和离群值检验进行MR分析。在逆方差加权法(优势比[OR]:0.667,95%置信区间[CI]:0.548 - 0.812,<0.001)、MR-Egger法(OR:0.647,95%CI:0.458 - 0.913,=0.019)和加权中位数法(OR:0.650,95%CI:0.466 - 0.908,=0.012)中发现了代谢物对VD有正向作用的有力证据。MR分析表明,代谢物(N6-苏氨甲酰腺苷[tA])可能与对VD的正向因果关联有关。