PDF(Pubmed)
Abstract：
UNASSIGNED: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.
UNASSIGNED: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.
UNASSIGNED: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).
UNASSIGNED: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.
UNASSIGNED: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.
UNASSIGNED: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).
UNASSIGNED: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.
摘要：
■观察性研究表明端粒长度（TL）和血脂（BL）水平之间存在关联。然而，这两个特征之间的因果关系尚不清楚.我们旨在通过孟德尔随机化（MR）阐明遗传预测的TL是否与BL水平相关，反之亦然。
■我们获得了与TL，甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C），高密度脂蛋白胆固醇（HDL-C），来自大规模全基因组关联研究（GWAS）的载脂蛋白A-1（ApoA-1）和载脂蛋白B（ApoB）。通过双向MR研究了TL和BL之间的因果关系，多变量MR和中介分析方法。采用逆方差加权(IVW)方法作为主要方法，辅之以其他几个估计器，以增强分析的稳健性。
■在正向MR分析中，我们确定了遗传预测的TL与TG水平之间的显着正相关（β=0.04，95％置信区间[CI]：0.01至0.06，p=0.003）。在反向MR分析中，TG（β=0.02，95％CI：0.01至0.03，p=0.004），LDL-C(β=0.03,95%CI:0.01~0.04,p=0.001)和ApoB(β=0.03,95%CI:0.01~0.04,p=9.71×10-5)与TL呈显著正相关,尽管在多变量MR分析中未观察到这种关系。通过两步MR进行的调解分析显示，在TG和TL的分析中，肥胖相关表型没有明显的调解作用，而LDL-C对TL的影响部分由体重指数（BMI）反向介导，介导比例为12.83%（95%CI：0.62%至25.04%）。
■我们的研究表明，较长的TL与较高的TG水平相关，而反过来,较高的TG，LDL-C,ApoB水平预测了更长的TL，BMI部分介导了这些影响。我们的发现为制定专门针对TL相关衰老和年龄相关疾病的预防策略和干预措施提供了宝贵的见解。
■我们获得了与TL，甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C），高密度脂蛋白胆固醇（HDL-C），来自大规模全基因组关联研究（GWAS）的载脂蛋白A-1（ApoA-1）和载脂蛋白B（ApoB）。通过双向MR研究了TL和BL之间的因果关系，多变量MR和中介分析方法。采用逆方差加权(IVW)方法作为主要方法，辅之以其他几个估计器，以增强分析的稳健性。
■在正向MR分析中，我们确定了遗传预测的TL与TG水平之间的显着正相关（β=0.04，95％置信区间[CI]：0.01至0.06，p=0.003）。在反向MR分析中，TG（β=0.02，95％CI：0.01至0.03，p=0.004），LDL-C(β=0.03,95%CI:0.01~0.04,p=0.001)和ApoB(β=0.03,95%CI:0.01~0.04,p=9.71×10-5)与TL呈显著正相关,尽管在多变量MR分析中未观察到这种关系。通过两步MR进行的调解分析显示，在TG和TL的分析中，肥胖相关表型没有明显的调解作用，而LDL-C对TL的影响部分由体重指数（BMI）反向介导，介导比例为12.83%（95%CI：0.62%至25.04%）。
■我们的研究表明，较长的TL与较高的TG水平相关，而反过来,较高的TG，LDL-C,ApoB水平预测了更长的TL，BMI部分介导了这些影响。我们的发现为制定专门针对TL相关衰老和年龄相关疾病的预防策略和干预措施提供了宝贵的见解。
