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

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 = ~ 23,00...

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Detalhes bibliográficos
Autores: Gao, Yixin, Wang, Ting|||0000-0002-6800-242X, Yu, Xinghao, Ferrari, Raffaele, Hernandez, Dena G.|||0000-0002-0188-9927, Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan|||0000-0002-7598-2892, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R.|||0000-0003-2967-9662, Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel|||0000-0001-8119-393X, Ruiz Laza, Agustín|||0000-0003-2633-2495, Boada, Mercè|||0000-0003-2617-3009, Borroni, Barbara|||0000-0001-9340-9814, Padovani, Alessandro|||0000-0002-0119-3639, Cruchaga, Carlos|||0000-0002-0276-2899, Cairns, Nigel J., Benussi, Luisa|||0000-0003-2836-8141, Binetti, Giuliano|||0000-0003-2759-5844, Ghidoni, Roberta|||0000-0002-7691-1957, Forloni, Gianluigi, Albani, Diego|||0000-0002-7050-6723, Galimberti, Daniela|||0000-0002-9284-5953, Fenoglio, Chiara|||0000-0001-6332-4721, Serpente, Maria, Scarpini, Elio|||0000-0002-6395-2119, Clarimón, Jordi|||0000-0002-6824-6942, Lleó, Alberto|||0000-0002-2568-5478, Blesa, Rafael|||0000-0003-4026-2884, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging-Yuek R., Mann, David M. A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes|||0000-0003-1636-1700, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, Pietro, Huey, Edward D., Wassermann, E. M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau|||0000-0002-7493-8777, Razquín, Cristina|||0000-0003-3480-2645, Ortega-Cubero, Sara|||0000-0003-0520-9439, Alonso, Elena, Perneczky, Robert|||0000-0003-1981-7435, Diehl-Schmid, Janine|||0000-0002-7745-1382, Alexopoulos, Panagiotis|||0000-0002-9047-6365, Kurz, Alexander, Rainero, Innocenzo|||0000-0001-6074-9628, Rubino, Elisa|||0000-0002-7553-7553, Pinessi, Lorenzo, Rogaeva, Ekaterina, St George Hyslop, Peter|||0000-0003-0796-7209, Rossi, Giacomina|||0000-0001-6680-2725, Tagliavini, Fabrizio|||0000-0003-1039-7315, Giaccone, Giorgio|||0000-0002-4803-0802, Rowe, James B., Schlachetzki, Johannes C. M., Uphill, J., Collinge, John, Mead, Simon|||0000-0002-4326-1468, Danek, Adrian|||0000-0001-8857-5383, Van Deerlin, Vivianna|||0000-0002-7400-9097, Grossman, Murray|||0000-0002-7447-6218, Trojanowski, John Q.|||0000-0002-9239-8794, Van der Zee, Julie|||0000-0003-4381-8040, Cruts, Marc|||0000-0002-1338-992X, Van Broeckhoven, Christine|||0000-0003-0183-7665, Cappa, Stefano F., Leber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis|||0000-0002-0941-3990, Nacmias, Benedetta|||0000-0001-9338-9040, Sorbi, Sandro|||0000-0002-0380-6670, Bagnoli, Silvia, Piaceri, Irene|||0000-0001-6787-2223, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C.|||0000-0002-6660-657X, Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw|||0000-0002-5473-3774, Rizzu, Patrizia, Heutink, Peter|||0000-0001-5218-1737, Snowden, Julie S., Rollinson, Sara|||0000-0002-0921-4318, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia|||0000-0003-3471-3343, Maletta, Raffaele|||0000-0002-0758-1835, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W.|||0000-0001-7189-7917, Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley, Parisi, Joseph E., Seeley, William W., Miller, Bruce L.|||0000-0002-2152-4220, Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G. P., Seelaar, Harro|||0000-0003-1989-7527, Pijnenburg, Yolande|||0000-0003-2464-1905, Scheltens, Philip|||0000-0002-1046-6408, Logroscino, Giancarlo|||0000-0003-0423-3242, Capozzo, Rosa|||0000-0002-7672-8669, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline|||0000-0002-9949-2951, Pasquier, Florence|||0000-0001-9880-9788, Rollin, Adeline, Deramecourt, Vincent, Lebouvier, Thibaud, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, S.|||0000-0003-1561-6054, Singleton, Andrew B.|||0000-0001-5606-700X, Hardy, John|||0000-0002-3122-0423, Momeni, Parastoo, Zhao, Huashuo, Zeng, Ping
Tipo de documento: artigo
Data de publicação:2020
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:283718
Acesso em linha:https://ddd.uab.cat/record/283718
https://dx.doi.org/urn:doi:10.1038/s41598-020-68848-9
Access Level:Acceso aberto
Palavra-chave:Computational biology and bioinformatics
Genetics
Medical research
Neurology
Risk factors
Descrição
Resumo: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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