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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

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Gao, Yixin 
Wang, Ting 
Yu, Xinghao 
Zhao, Huashuo 
Zeng, Ping 


Abstract: 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.


Funder: QingLan Research Project of Jiangsu for Outstanding Young Teachers

Funder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical University

Funder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical University


Article, /631/114, /631/208, /692/308, /692/617, /692/499, article

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Scientific Reports

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Nature Publishing Group UK
Youth Foundation of Humanity and Social Science funded by Ministry of Education of China (18YJC910002)
Natural Science Foundation of Jiangsu Province (BK20181472)
China Postdoctoral Science Foundation (2018M630607, 2019T120465)
Six-Talent Peaks Project in Jiangsu of China (WSN-087)
Social Development Project of Xuzhou (KC19017)
National Natural Science Foundation of China (81402765)
Statistical Science Research Project from National Bureau of Statistics of China (2014LY112)