Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.
Center for Medical Statistics and Data Analysis, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.
Sci Rep. 2020 Jul 22;10(1):12184. doi: 10.1038/s41598-020-68848-9.
We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93-1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53-1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
我们采用孟德尔随机化（MR）方法，利用全基因组关联研究的汇总统计数据（欧洲人群中白细胞端粒长度（LTL）和肌萎缩侧索硬化症（ALS）的 ~38000 例和 ~81000 例；亚洲人群中 LTL 和 ALS 的 ~23000 例和 ~4100 例）来评估 LTL 与 ALS 之间的因果关系。我们进一步评估了脂质在 LTL 向 ALS 通路中的中介作用。欧洲人群中 LTL 每标准偏差降低时 ALS 的比值比为 1.10（95%CI 0.93-1.31，p=0.274），亚洲人群中 LTL 每标准偏差降低时 ALS 的比值比为 0.75（95%CI 0.53-1.07，p=0.116）。在欧洲人群中，LTL 与额颞叶痴呆之间也存在这种无关联。然而，我们发现 LTL 对 ALS 的间接影响可能通过欧洲人群中的低密度脂蛋白（LDL）或总胆固醇（TC）来介导。这些结果在广泛的敏感性分析中仍然稳健。总体而言，我们的 MR 研究既不支持 LTL 与两种人群中 ALS 风险之间的直接因果关系，也没有提供 LDL 或 TC 对 LTL 和 ALS 影响的中介作用的明确证据，但在欧洲人群中提供了提示性证据。
