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Telomere length and metabolic syndrome traits: A Mendelian randomisation study
Aging Cell ( IF 8.0 ) Pub Date : 2021-07-27 , DOI: 10.1111/acel.13445
Nellie Y Loh 1 , Raymond Noordam 2 , Constantinos Christodoulides 1
Affiliation  

Observational studies have revealed associations between short leucocyte telomere length (LTL), a TL marker in somatic tissues and multiple Metabolic Syndrome (MetS) traits. Animal studies have supported these findings by showing that increased telomere attrition leads to adipose tissue dysfunction and insulin resistance. We investigated the associations between genetically instrumented LTL and MetS traits using Mendelian Randomisation (MR). Fifty-two independent variants identified at FDR<0.05 from a genome-wide association study (GWAS) including 78,592 Europeans and collectively accounting for 2.93% of LTL variance were selected as genetic instruments for LTL. Summary-level data for MetS traits and for the MetS as a binary phenotype were obtained from the largest publicly available GWAS and two-sample MR analyses were used to estimate the associations of LTL with these traits. The combined effect of the genetic instruments was modelled using inverse variance weighted regression and sensitivity analyses with MR-Egger, weighted-median and MR-PRESSO were performed to test for and correct horizonal pleiotropy. Genetically instrumented longer LTL was associated with higher waist-to-hip ratio adjusted for body mass index (β = 0.045 SD, SE = 0.018, p = 0.01), raised systolic (β = 1.529 mmHg, SE = 0.332, p = 4x10−6) and diastolic (β = 0.633 mmHg, SE = 0.222, p = 0.004) blood pressure, and increased MetS risk (OR = 1.133, 95% CI 1.057–1.215). Consistent results were obtained in sensitivity analyses, which provided no evidence of unbalanced horizontal pleiotropy. Telomere shortening might not be a major driver of cellular senescence and dysfunction in human adipose tissue. Future experimental studies should examine the mechanistic bases for the links between longer LTL and increased upper-body fat distribution and raised blood pressure.

中文翻译:

端粒长度和代谢综合征特征:孟德尔随机化研究

观察性研究揭示了短白细胞端粒长度 (LTL)、体细胞组织中的 TL 标记和多种代谢综合征 (MetS) 特征之间的关联。动物研究表明端粒磨损增加会导致脂肪组织功能障碍和胰岛素抵抗,从而支持了这些发现。我们使用孟德尔随机化 (MR) 研究了基因检测 LTL 和 MetS 性状之间的关联。从包括 78,592 名欧洲人在内的全基因组关联研究 (GWAS) 中鉴定的 FDR<0.05 的 52 个独立变体被选为 LTL 变异的 2.93%。MetS 性状和作为二元表型的 MetS 的汇总水平数据是从最大的公开可用的 GWAS 中获得的,并且使用两样本 MR 分析来估计 LTL 与这些性状的关联。使用逆方差加权回归对遗传工具的组合效应进行建模,并使用 MR-Egger、加权中值和 MR-PRESSO 进行敏感性分析以测试和纠正水平多效性。基因检测的较长 LTL 与根据体重指数调整后的较高腰臀比相关。β  = 0.045 SD, SE = 0.018, p  = 0.01),收缩压升高 ( β  = 1.529 mmHg, SE = 0.332, p = 4x10 -6 ) 和舒张压 ( β  = 0.633 mmHg, SE = 0.222, p  = 0.004) 血压, 并增加了 MetS 风险 (OR = 1.133, 95% CI 1.057–1.215)。在敏感性分析中获得了一致的结果,没有提供不平衡水平多效性的证据。端粒缩短可能不是人类脂肪组织细胞衰老和功能障碍的主要驱动因素。未来的实验研究应该检查更长的 LTL 与增加的上身脂肪分布和血压升高之间的联系的机制基础。
更新日期:2021-08-19
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