TY - JOUR
T1 - Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
AU - International FTD-Genomics Consortium (IFGC)
AU - Gao, Yixin
AU - Wang, Ting
AU - Yu, Xinghao
AU - Ferrari, Raffaele
AU - Hernandez, Dena G.
AU - Nalls, Michael A.
AU - Rohrer, Jonathan D.
AU - Ramasamy, Adaikalavan
AU - Kwok, John B.J.
AU - Dobson-Stone, Carol
AU - Brooks, William S.
AU - Schofield, Peter R.
AU - Halliday, Glenda M.
AU - Hodges, John R.
AU - Piguet, Olivier
AU - Bartley, Lauren
AU - Thompson, Elizabeth
AU - Haan, Eric
AU - Hernández, Isabel
AU - Ruiz, Agustín
AU - Boada, Mercè
AU - Borroni, Barbara
AU - Padovani, Alessandro
AU - Cruchaga, Carlos
AU - Cairns, Nigel J.
AU - Benussi, Luisa
AU - Binetti, Giuliano
AU - Ghidoni, Roberta
AU - Forloni, Gianluigi
AU - Albani, Diego
AU - Galimberti, Daniela
AU - Fenoglio, Chiara
AU - Serpente, Maria
AU - Scarpini, Elio
AU - Clarimón, Jordi
AU - Lleó, Alberto
AU - Blesa, Rafael
AU - Waldö, Maria Landqvist
AU - Nilsson, Karin
AU - Nilsson, Christer
AU - Mackenzie, Ian R.A.
AU - Hsiung, Ging Yuek R.
AU - Mann, David M.A.
AU - Grafman, Jordan
AU - Morris, Christopher M.
AU - Attems, Johannes
AU - Griffiths, Timothy D.
AU - McKeith, Ian G.
AU - Thomas, Alan J.
AU - Pietrini, Pietro
N1 - Funding Information:
We thank the ENGAGE Telomere Consortium, AVS, IFGC and all other GWAS consortium studies for making summary statistics datasets publicly available for us and are grateful to all the investigators and participants who contributed to those studies. Further acknowledgements for IFGC can be found in the Supplementary Acknowledgment. This study was supported by Youth Foundation of Humanity and Social Science funded by Ministry of Education of China (18YJC910002), the Natural Science Foundation of Jiangsu (BK20181472), the China Postdoctoral Science Foundation (2018M630607 and 2019T120465), the QingLan Research Project of Jiangsu for Outstanding Young Teachers, the Six-Talent Peaks Project in Jiangsu of China (WSN-087), the Social Development Project of Xuzhou (KC19017), the Project funded by Postdoctoral Science Foundation of Xuzhou Medical University, the National Natural Science Foundation of China (81402765), the Statistical Science Research Project from National Bureau of Statistics of China (2014LY112) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical University.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-020-68848-9
DO - 10.1038/s41598-020-68848-9
M3 - Article
C2 - 32699404
AN - SCOPUS:85088385622
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 12184
ER -