TY - JOUR
T1 - Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
T2 - Scientific Reports
AU - Gao, Y.
AU - Wang, T.
AU - Yu, X.
AU - International FTD-Genomics Consortium (IFGC)
AU - Ferrari, R.
AU - Hernandez, D.G.
AU - Nalls, M.A.
AU - Rohrer, J.D.
AU - Ramasamy, A.
AU - Kwok, J.B.J.
AU - Dobson-Stone, C.
AU - Brooks, W.S.
AU - Schofield, P.R.
AU - Halliday, G.M.
AU - Hodges, J.R.
AU - Piguet, O.
AU - Bartley, L.
AU - Thompson, E.
AU - Haan, E.
AU - Hernández, I.
AU - Ruiz, A.
AU - Boada, M.
AU - Borroni, B.
AU - Padovani, A.
AU - Cruchaga, C.
AU - Cairns, N.J.
AU - Benussi, L.
AU - Binetti, G.
AU - Ghidoni, R.
AU - Forloni, G.
AU - Albani, D.
AU - Galimberti, D.
AU - Fenoglio, C.
AU - Serpente, M.
AU - Scarpini, E.
AU - Clarimón, J.
AU - Lleó, A.
AU - Blesa, R.
AU - Waldö, M.L.
AU - Nilsson, K.
AU - Nilsson, C.
AU - Rossi, G.
AU - Tagliavini, F.
AU - Giaccone, G.
AU - Cappa, S.F.
AU - Sorbi, S.
AU - Bernardi, L.
AU - Gallo, M.
AU - Novelli, V.
AU - Puca, A.A.
AU - Franceschi, M.
AU - Zhao, Huashuo
AU - Zeng, Ping
N1 - Export Date: 20 August 2020
Correspondence Address: Zhao, H.; Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical University, Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical UniversityChina; email: hszhao@xzhmu.edu.cn
PY - 2020
Y1 - 2020
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.
U2 - 10.1038/s41598-020-68848-9
DO - 10.1038/s41598-020-68848-9
M3 - Article
VL - 10
JO - Sci. Rep.
JF - Sci. Rep.
SN - 2045-2322
IS - 1
M1 - 12184
ER -