Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
Gao, Yixin (Xuzhou Medical University)
Wang, Ting (Xuzhou Medical University)
Yu, Xinghao (Xuzhou Medical University)
Ferrari, Raffaele (Russell Square House)
Hernandez, Dena G. (Queen Square)
Nalls, Michael A. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Rohrer, Jonathan D. (Queen Square)
Ramasamy, Adaikalavan (University of Oxford)
Kwok, John B.J. (University of New South Wales)
Dobson-Stone, Carol (University of New South Wales)
Brooks, William S. (University of New South Wales)
Schofield, Peter R. (Neuroscience Research Australia)
Halliday, Glenda M. (Neuroscience Research Australia)
Hodges, John R. (Neuroscience Research Australia)
Piguet, Olivier (Neuroscience Research Australia)
Bartley, Lauren (Neuroscience Research Australia)
Thompson, Elizabeth (University of Adelaide)
Haan, Eric (University of Adelaide)
Hernández, Isabel (Institut Català de Neurociéncies Aplicades)
Ruiz, Agustín (Institut Català de Neurociéncies Aplicades)
Boada, Mercè (Institut Català de Neurociéncies Aplicades)
Borroni, Barbara (University of Brescia)
Padovani, Alessandro (University of Brescia)
Cruchaga, Carlos (Washington University School of Medicine)
Cairns, Nigel J. (Washington University)
Benussi, Luisa (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Binetti, Giuliano (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Ghidoni, Roberta (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Forloni, Gianluigi (IRCCS Istituto di Ricerche Farmacologiche. "Mario Negri")
Albani, Diego (IRCCS Istituto di Ricerche Farmacologiche. "Mario Negri")
Galimberti, Daniela (IRCCS Ospedale Maggiore Policlinico)
Fenoglio, Chiara (IRCCS Ospedale Maggiore Policlinico)
Serpente, Maria (IRCCS Ospedale Maggiore Policlinico)
Scarpini, Elio (University of Milan)
Clarimón, Jordi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Blesa, Rafael (Institut d'Investigació Biomèdica Sant Pau)
Waldö, Maria Landqvist (Lund University)
Nilsson, Karin (Lund University)
Nilsson, Christer (Lund University)
Mackenzie, Ian R.A. (University of British Columbia)
Hsiung, Ging-Yuek R. (University of British Columbia)
Mann, David M. A. (Salford Royal Hospital)
Grafman, Jordan (Northwestern University)
Morris, Christopher M. (Newcastle University)
Attems, Johannes (Newcastle University)
Griffiths, Timothy D. (Newcastle University Medical School)
McKeith, Ian G. (Newcastle University)
Thomas, Alan J. (Newcastle University)
Pietrini, Pietro (IMT School for Advanced Studies)
Huey, Edward D. (Columbia University)
Wassermann, Eric M. (National Insititutes of Health)
Baborie, Atik (University of Alberta Edmonton)
Jaros, Evelyn (Newcastle University)
Tierney, Michael C. (National Insititutes of Health)
Pastor, Pau (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Razquin, Cristina (Universidad de Navarra)
Ortega-Cubero, Sara (Universidad de Navarra)
Alonso, Elena (Universidad de Navarra)
Perneczky, Robert (West London Mental Health Trust)
Diehl-Schmid, Janine (Technische Universität München)
Alexopoulos, Panagiotis (Technische Universität München)
Kurz, Alexander (Technische Universität München)
Rainero, Innocenzo (A.O. Città della Salute e della Scienza di Torino)
Rubino, Elisa (A.O. Città della Salute e della Scienza di Torino)
Pinessi, Lorenzo (A.O. Città della Salute e della Scienza di Torino)
Rogaeva, Ekaterina (University of Toronto)
St George Hyslop, Peter (University of Cambridge)
Rossi, Giacomina (Fondazione IRCCS Istituto Neurologico Carlo Besta)
Tagliavini, Fabrizio (Fondazione IRCCS Istituto Neurologico Carlo Besta)
Giaccone, Giorgio (Fondazione IRCCS Istituto Neurologico Carlo Besta)
Rowe, James B. (Behavioural and Clinical Neuroscience Institute)
Schlachetzki, Johannes C. M. (University of California San Diego)
Uphill, James (University College London. Institute of Neurology)
Collinge, John (University College London. Institute of Neurology)
Mead, Simon (University College London. Institute of Neurology)
Danek, Adrian (German Center for Neurodegenerative Diseases (DZNE))
Van Deerlin, Vivianna M. (University of Pennsylvania Perelman School of Medicine)
Grossman, Murray (University of Pennsylvania Perelman School of Medicine)
Trojanowski, John Q. (University of Pennsylvania Perelman School of Medicine)
van der Zee, Julie (University of Antwerp)
Cruts, Marc (University of Antwerp)
Van Broeckhoven, Christine (University of Antwerp)
Cappa, Stefano F. (Vita-Salute University and San Raffaele Scientific Institute)
Leber, Isabelle (CNRS UMR 7225)
Hannequin, Didier (Rouen University Hospital (França))
Golfier, Véronique (CH Saint Brieuc)
Vercelletto, Martine (CHU Nantes)
Brice, Alexis (AP-HP. Hôpital de la Salpêtrière)
Nacmias, Benedetta (University of Florence)
Sorbi, Sandro (University of Florence and IRCCS "Don Carlo Gnocchi" Firenze)
Bagnoli, Silvia (University of Florence)
Piaceri, Irene (University of Florence)
Nielsen, Jørgen E. (Copenhagen University Hospital)
Hjermind, Lena E. (University of Copenhagen)
Riemenschneider, Matthias (Saarland University)
Mayhaus, Manuel (Saarland University)
Ibach, Bernd (University Regensburg)
Gasparoni, Gilles (Saarland University)
Pichler, Sabrina (Saarland University)
Gu, Wei (University of Luxembourg)
Rossor, Martin N. (Queen Square)
Fox, Nick C. (University College London Queen Square Institute of Neurology. Dementia Research Centre)
Warren, Jason D. (Queen Square)
Spillantini, Maria Grazia (University of Cambridge)
Morris, Huw R. (Russell Square House)
Rizzu, Patrizia (German Center for Neurodegenerative Diseases-Tübingen)
Heutink, Peter (German Center for Neurodegenerative Diseases-Tübingen)
Snowden, Julie S. (University of Manchester)
Rollinson, Sara (University of Manchester)
Richardson, Anna (University of Manchester)
Gerhard, Alexander (The University of Manchester)
Bruni, Amalia C. (ASPCZ)
Maletta, Raffaele (ASPCZ)
Frangipane, Francesca (ASPCZ)
Cupidi, Chiara (ASPCZ)
Bernardi, Livia (ASPCZ)
Anfossi, Maria (ASPCZ)
Gallo, Maura (ASPCZ)
Conidi, Maria Elena (ASPCZ)
Smirne, Nicoletta (ASPCZ)
Rademakers, Rosa (Mayo Clinic Jacksonville)
Baker, Matt (Mayo Clinic Jacksonville)
Dickson, Dennis W. (Mayo Clinic Jacksonville)
Graff-Radford, Neill R. (Mayo Clinic Jacksonville)
Petersen, Ronald C. (Mayo Clinic Rochester)
Knopman, David (Mayo Clinic Rochester)
Josephs, Keith A. (Mayo Clinic Rochester)
Boeve, Bradley (Mayo Clinic Rochester)
Parisi, Joseph E. (Mayo Clinic Rochester)
Seeley, William W. (University of California)
Miller, Bruce L. (University of California)
Karydas, Anna M. (University of California)
Rosen, Howard (University of California)
van Swieten, John C. (VU University Medical Centre)
Dopper, Elise G. P. (Erasmus Medical Centre)
Seelaar, Harro (Erasmus Medical Centre)
Pijnenburg, Yolande A. L. (VU University Medical Centre)
Scheltens, Philip (VU University Medical Centre)
Logroscino, Giancarlo (University of Bari)
Capozzo, Rosa (University of Bari)
Novelli, Valeria (Fondazione Policlinico Universitario A. Gemelli)
Puca, Annibale A. (University of Salerno)
Franceschi, Massimo (IRCCS Multimedica)
Postiglione, Alfredo (University of Naples Federico II)
Milan, Graziella (Geriatric Center Frullone- ASL Napoli 1 Centro)
Sorrentino, Paolo (Geriatric Center Frullone- ASL Napoli 1 Centro)
Kristiansen, Mark (Institute of Child Health (ICH))
Chiang, Huei-Hsin (Karolinska University Hospital and Karolinska Institutet (Suecia))
Graff, Caroline (Karolinska University Hospital and Karolinska Institutet (Suecia))
Pasquier, Florence (Univ Lille)
Rollin, Adeline (Univ Lille)
Deramecourt, Vincent (Univ Lille)
Lebouvier, Thibaud (Univ Lille)
Kapogiannis, Dimitrios (National Institute on Aging (NIA/NIH))
Ferrucci, Luigi (National Institute on Aging (Baltimore, Estats Units d'Amèrica))
Pickering-Brown, S. (University of Manchester)
Singleton, Andrew B. (National Institute on Aging (Bethesda, Estats Units d'Amèrica))
Hardy, John (Russell Square House)
Momeni, Parastoo (Texas Tech University Health Science Center)
Zhao, Huashuo (Xuzhou Medical University)
Zeng, Ping (Xuzhou Medical University)
Universitat Autònoma de Barcelona

Date:	2020
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Computational biology and bioinformatics ; Genetics ; Medical research ; Neurology ; Risk factors
Published in:	Scientific reports, Vol. 10 Núm. 1 (january 2020) , p. 12184, ISSN 2045-2322

DOI: 10.1038/s41598-020-68848-9
PMID: 32699404

12 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles