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; Didier Hannequin; Véronique Golfier; Martine Vercelletto; Alexis Brice; 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; Ping Zeng

doi:10.1038/s41598-020-68848-9

Journal Articles Scientific Reports Year : 2020

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

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1
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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

Isabelle Leber

Function : Author

Institut du Cerveau = Paris Brain Institute

Didier Hannequin

Function : Author

Véronique Golfier

Function : Author

Martine Vercelletto

Function : Author

Alexis Brice

Function : Author
PersonId : 1104774
ORCID : 0000-0002-0941-3990
IdRef : 050512935

Institut du Cerveau = Paris Brain Institute

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
PersonId : 754049
IdHAL : thibaud-lebouvier
ORCID : 0000-0002-6630-394X
IdRef : 177112190

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

Xuzhou Medical University

Ping Zeng

Function : Author

Xuzhou Medical University

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.

Domains

Human health and pathology

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s41598-020-68848-9.pdf (1.18 Mo)

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https://hal.sorbonne-universite.fr/hal-04538531

Submitted on : Tuesday, April 9, 2024-11:50:08 AM

Last modification on : Tuesday, July 23, 2024-4:33:04 PM

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

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HAL Id : hal-04538531 , version 1
DOI : 10.1038/s41598-020-68848-9
PUBMED : 32699404
PUBMEDCENTRAL : PMC7376149

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

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