Leukocyte Telomere Length Shortening and Alzheimer's Disease Etiology
Leukocyte Telomere Length Shortening and Alzheimer's Disease Etiology
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DOI：
10.3233/jad-190134
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Yu, Haining
中科院分区：
文献类型：
--
作者：
Guo, Yanfang;Yu, Haining
背景：一些观察性研究发现白细胞端粒长度（TL）与阿尔茨海默病（AD）或痴呆相关。然而，这些发现是基于小样本量，不能澄清这种关系是否是因果关系。全基因组关联研究（GWAS）已经确定了与TL相关的常见变异，为使用孟德尔随机化（MR）方法检查TL对AD的因果效应提供了宝贵的资源。目的：使用GWAS汇总统计量检查TL是否与AD因果相关。使用由与白细胞TL相关的七种变体组成的遗传风险评分作为工具变量，我们通过对总结的全基因组关联研究数据应用MR方法来检验较短的TL是否与较高的AD风险相关。结果：TL的遗传风险评分与较高的AD风险相关[对于每个TL降低的等位基因，对数优势比（OR）= 0.003; 95%置信区间（CI）：0.001，0.005，p = 0.005]。此外，MR分析提供了支持，较短的TL与AD的风险较高的因果关系（log-OR = 0.04每SD减少TL; 95%CI：0.01，0.08，p = 0.01）。
Background: Several observational studies have found leukocyte telomere length (TL) to be associated with Alzheimer's diseases (AD) or dementia. However, these findings were based on small sample sizes and cannot clarify whether this relationship was causal. Genome-wide association studies (GWAS) have identified common variants associated with TL, providing a valuable resource for examining the causal effect of TL on AD using Mendelian Randomization (MR) methods.Objective: To examine if TL was causally associated with AD using GWAS summary statistics.Methods: Using a genetic risk score comprised of seven variants associated with leukocyte TL as an instrumental variable, we tested whether shorter TL was associated with a higher risk of AD by applying an MR approach to the summarized genome-wide association study data.Results: The genetic risk score for TL was associated with higher risk of AD [log-odds ratio (OR) = 0.003 for per TL-decreasing allele; 95% confidence interval (CI): 0.001, 0.005, p = 0.005]. Moreover, the MR analysis provided support for shorter TL to be causally associated with a higher risk of AD (log-OR = 0.04 per SD-decrease of TL; 95% CI: 0.01, 0.08, p = 0.01).Conclusion: We suggest that TL has a causal effect on the risk of AD.