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Journal Articles Scientific Reports Year : 2020

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

Yixin Gao , Ting Wang , Xinghao Yu , Raffaele Ferrari , Dena G Hernandez , Michael A Nalls , Jonathan D Rohrer , Adaikalavan Ramasamy , John B J Kwok , Carol Dobson-Stone , William S Brooks , Peter R Schofield , Glenda M Halliday , John R Hodges , Olivier Piguet , Lauren Bartley , Elizabeth Thompson , Eric Haan , Isabel Hernández , Agustín Ruiz , Mercè Boada , Barbara Borroni , Alessandro Padovani , Carlos Cruchaga , Nigel J Cairns , Luisa Benussi , Giuliano Binetti , Roberta Ghidoni , Gianluigi Forloni , Diego Albani , Daniela Galimberti , Chiara Fenoglio , Maria Serpente , Elio Scarpini , Jordi Clarimón , Alberto Lleó , Rafael Blesa , Maria Landqvist Waldö , Karin Nilsson , Christer Nilsson , Ian R A Mackenzie , Ging-Yuek Hsiung , David M A Mann , Jordan Grafman , Christopher M Morris , Johannes Attems , Timothy D Griffiths , Ian G Mckeith , Alan J Thomas , Pietro Pietrini , Edward D Huey , Eric M Wassermann , Atik Baborie , Evelyn Jaros , Michael C Tierney , Pau Pastor , Cristina Razquin , Sara Ortega-Cubero , Elena Alonso , Robert Perneczky , Janine Diehl-Schmid , Panagiotis Alexopoulos , Alexander Kurz , Innocenzo Rainero , Elisa Rubino , Lorenzo Pinessi , Ekaterina Rogaeva , Peter St George-Hyslop , Giacomina Rossi , Fabrizio Tagliavini , Giorgio Giaccone , James B Rowe , Johannes C M Schlachetzki , James Uphill , John Collinge , Simon Mead , Adrian Danek , Vivianna M van Deerlin , Murray Grossman , John Q Trojanowski , Julie van der Zee , Marc Cruts , Christine van Broeckhoven , Stefano F Cappa , Isabelle Leber (1) , Didier Hannequin , Véronique Golfier , Martine Vercelletto , Alexis Brice (1) , Benedetta Nacmias , Sandro Sorbi , Silvia Bagnoli , Irene Piaceri , Jørgen E Nielsen , Lena E Hjermind , Matthias Riemenschneider , Manuel Mayhaus , Bernd Ibach , Gilles Gasparoni , Sabrina Pichler , Wei Gu , Martin N Rossor , Nick C Fox , Jason D Warren , Maria Grazia Spillantini , Huw R Morris , Patrizia Rizzu , Peter Heutink , Julie S Snowden , Sara Rollinson , Anna Richardson , Alexander Gerhard , Amalia C Bruni , Raffaele Maletta , Francesca Frangipane , Chiara Cupidi , Livia Bernardi , Maria Anfossi , Maura Gallo , Maria Elena Conidi , Nicoletta Smirne , Rosa Rademakers , Matt Baker , Dennis W Dickson , Neill R Graff-Radford , Ronald C Petersen , David Knopman , Keith A Josephs , Bradley F Boeve , Joseph E Parisi , William W Seeley , Bruce L Miller , Anna M Karydas , Howard Rosen , John C van Swieten , Elise G P Dopper , Harro Seelaar , Yolande a L Pijnenburg , Philip Scheltens , Giancarlo Logroscino , Rosa Capozzo , Valeria Novelli , Annibale A Puca , Massimo Franceschi , Alfredo Postiglione , Graziella Milan , Paolo Sorrentino , Mark Kristiansen , Huei-Hsin Chiang , Caroline Graff , Florence Pasquier , Adeline Rollin , Vincent Deramecourt , Thibaud Lebouvier , Dimitrios Kapogiannis , Luigi Ferrucci , Stuart Pickering-Brown , Andrew B Singleton , John Hardy , Parastoo Momeni , Huashuo Zhao (2) , Ping Zeng (2)
Yixin Gao
  • Function : Author
Ting Wang
  • Function : Author
Xinghao Yu
  • Function : Author
Raffaele Ferrari
  • Function : Author
Dena G Hernandez
  • Function : Author
Michael A Nalls
  • Function : Author
Jonathan D Rohrer
  • Function : Author
Adaikalavan Ramasamy
  • Function : Author
John B J Kwok
  • Function : Author
Carol Dobson-Stone
  • Function : Author
William S Brooks
  • Function : Author
Peter R Schofield
  • Function : Author
Glenda M Halliday
  • Function : Author
John R Hodges
  • Function : Author
Olivier Piguet
  • Function : Author
Lauren Bartley
  • Function : Author
Elizabeth Thompson
  • Function : Author
Eric Haan
  • Function : Author
Isabel Hernández
  • Function : Author
Agustín Ruiz
  • Function : Author
Mercè Boada
  • Function : Author
Barbara Borroni
  • Function : Author
Alessandro Padovani
  • Function : Author
Carlos Cruchaga
  • Function : Author
Nigel J Cairns
  • Function : Author
Luisa Benussi
  • Function : Author
Giuliano Binetti
  • Function : Author
Roberta Ghidoni
  • Function : Author
Gianluigi Forloni
  • Function : Author
Diego Albani
  • Function : Author
Daniela Galimberti
  • Function : Author
Chiara Fenoglio
  • Function : Author
Maria Serpente
  • Function : Author
Elio Scarpini
  • Function : Author
Jordi Clarimón
  • Function : Author
Alberto Lleó
  • Function : Author
Rafael Blesa
  • Function : Author
Maria Landqvist Waldö
  • Function : Author
Karin Nilsson
  • Function : Author
Christer Nilsson
  • Function : Author
Ian R A Mackenzie
  • Function : Author
Ging-Yuek Hsiung
  • Function : Author
David M A Mann
  • Function : Author
Jordan Grafman
  • Function : Author
Christopher M Morris
  • Function : Author
Johannes Attems
  • Function : Author
Timothy D Griffiths
  • Function : Author
Ian G Mckeith
  • Function : Author
Alan J Thomas
  • Function : Author
Pietro Pietrini
  • Function : Author
Edward D Huey
  • Function : Author
Eric M Wassermann
  • Function : Author
Atik Baborie
  • Function : Author
Evelyn Jaros
  • Function : Author
Michael C Tierney
  • Function : Author
Pau Pastor
  • Function : Author
Cristina Razquin
  • Function : Author
Sara Ortega-Cubero
  • Function : Author
Elena Alonso
  • Function : Author
Robert Perneczky
  • Function : Author
Janine Diehl-Schmid
  • Function : Author
Panagiotis Alexopoulos
  • Function : Author
Alexander Kurz
  • Function : Author
Innocenzo Rainero
  • Function : Author
Elisa Rubino
  • Function : Author
Lorenzo Pinessi
  • Function : Author
Ekaterina Rogaeva
  • Function : Author
Peter St George-Hyslop
  • Function : Author
Giacomina Rossi
  • Function : Author
Fabrizio Tagliavini
  • Function : Author
Giorgio Giaccone
  • Function : Author
James B Rowe
  • Function : Author
Johannes C M Schlachetzki
  • Function : Author
James Uphill
  • Function : Author
John Collinge
  • Function : Author
Simon Mead
  • Function : Author
Adrian Danek
  • Function : Author
Vivianna M van Deerlin
  • Function : Author
Murray Grossman
  • Function : Author
John Q Trojanowski
  • Function : Author
Julie van der Zee
  • Function : Author
Marc Cruts
  • Function : Author
Christine van Broeckhoven
  • Function : Author
Stefano F Cappa
  • Function : Author
Didier Hannequin
  • Function : Author
Véronique Golfier
  • Function : Author
Martine Vercelletto
  • Function : Author
Benedetta Nacmias
  • Function : Author
Sandro Sorbi
  • Function : Author
Silvia Bagnoli
  • Function : Author
Irene Piaceri
  • Function : Author
Jørgen E Nielsen
  • Function : Author
Lena E Hjermind
  • Function : Author
Matthias Riemenschneider
  • Function : Author
Manuel Mayhaus
  • Function : Author
Bernd Ibach
  • Function : Author
Gilles Gasparoni
  • Function : Author
Sabrina Pichler
  • Function : Author
Wei Gu
  • Function : Author
Martin N Rossor
  • Function : Author
Nick C Fox
  • Function : Author
Jason D Warren
  • Function : Author
Maria Grazia Spillantini
  • Function : Author
Huw R Morris
  • Function : Author
Patrizia Rizzu
  • Function : Author
Peter Heutink
  • Function : Author
Julie S Snowden
  • Function : Author
Sara Rollinson
  • Function : Author
Anna Richardson
  • Function : Author
Alexander Gerhard
  • Function : Author
Amalia C Bruni
  • Function : Author
Raffaele Maletta
  • Function : Author
Francesca Frangipane
  • Function : Author
Chiara Cupidi
  • Function : Author
Livia Bernardi
  • Function : Author
Maria Anfossi
  • Function : Author
Maura Gallo
  • Function : Author
Maria Elena Conidi
  • Function : Author
Nicoletta Smirne
  • Function : Author
Rosa Rademakers
  • Function : Author
Matt Baker
  • Function : Author
Dennis W Dickson
  • Function : Author
Neill R Graff-Radford
  • Function : Author
Ronald C Petersen
  • Function : Author
David Knopman
  • Function : Author
Keith A Josephs
  • Function : Author
Bradley F Boeve
  • Function : Author
Joseph E Parisi
  • Function : Author
William W Seeley
  • Function : Author
Bruce L Miller
  • Function : Author
Anna M Karydas
  • Function : Author
Howard Rosen
  • Function : Author
John C van Swieten
  • Function : Author
Elise G P Dopper
  • Function : Author
Harro Seelaar
  • Function : Author
Yolande a L Pijnenburg
  • Function : Author
Philip Scheltens
  • Function : Author
Giancarlo Logroscino
  • Function : Author
Rosa Capozzo
  • Function : Author
Valeria Novelli
  • Function : Author
Annibale A Puca
  • Function : Author
Massimo Franceschi
  • Function : Author
Alfredo Postiglione
  • Function : Author
Graziella Milan
  • Function : Author
Paolo Sorrentino
  • Function : Author
Mark Kristiansen
  • Function : Author
Huei-Hsin Chiang
  • Function : Author
Caroline Graff
  • Function : Author
Florence Pasquier
  • Function : Author
Adeline Rollin
  • Function : Author
Vincent Deramecourt
  • Function : Author
Thibaud Lebouvier
  • Function : Author
Dimitrios Kapogiannis
  • Function : Author
Luigi Ferrucci
  • Function : Author
Stuart Pickering-Brown
  • Function : Author
Andrew B Singleton
  • Function : Author
John Hardy
  • Function : Author
Parastoo Momeni
  • Function : Author
Huashuo Zhao
  • Function : Author
  • PersonId : 1373014

Abstract

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.
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hal-04538531 , version 1 (09-04-2024)

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Yixin Gao, Ting Wang, Xinghao Yu, Raffaele Ferrari, Dena G Hernandez, et al.. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis. Scientific Reports, 2020, 10 (1), pp.12184. ⟨10.1038/s41598-020-68848-9⟩. ⟨hal-04538531⟩
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