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 - Diehl-Schmid, Janine
N1 - 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.
UR - https://www.scopus.com/pages/publications/85088385622
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 -