Journal article
Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
Scientific reports, Vol.10(1), 12184
07/22/2020
DOI: 10.1038/s41598-020-68848-9
PMCID: PMC7376149
PMID: 32699404
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=similar to 38,000 for LTL and similar to 81,000 for ALS in the European population; n=similar to 23,000 for LTL and similar to 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.
Details
- Title: Subtitle
- Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- Creators
- Yixin Gao - Xuzhou Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Xuzhou 221004, Jiangsu, Peoples R ChinaTing Wang - Xuzhou Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Xuzhou 221004, Jiangsu, Peoples R ChinaXinghao Yu - Xuzhou Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Xuzhou 221004, Jiangsu, Peoples R ChinaHuashuo Zhao - Xuzhou Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Xuzhou 221004, Jiangsu, Peoples R ChinaPing Zeng - Xuzhou Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Xuzhou 221004, Jiangsu, Peoples R ChinaRaffaele Ferrari - Nashotah House Theological SeminaryDena G. Hernandez - NIA, Lab Neurogenet, NIH, Bldg 35,Room 1A215,35 Convent Dr, Bethesda, MD 20892 USAMichael A. Nails - NIA, Lab Neurogenet, NIH, Bldg 35,Room 1A215,35 Convent Dr, Bethesda, MD 20892 USAJonathan D. Rohrers - UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, EnglandAdaikalavan Ramasamys - UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, EnglandJohn B. J. Kwok - Neurosci Res Australia, Sydney, NSW 2031, AustraliaCarol Dobson-Stone - Neurosci Res Australia, Sydney, NSW 2031, AustraliaWilliam S. Brooks - Neurosci Res Australia, Sydney, NSW 2031, AustraliaPeter R. Schofield - Neurosci Res Australia, Sydney, NSW 2031, AustraliaGlenda M. Halliday - Neurosci Res Australia, Sydney, NSW 2031, AustraliaJohn R. Hodges - Neurosci Res Australia, Sydney, NSW 2031, AustraliaOlivier Piguet - Neurosci Res Australia, Sydney, NSW 2031, AustraliaLauren Bartley - Neurosci Res Australia, Sydney, NSW 2031, AustraliaElizabeth Thompson - Womens & Childrens Hosp, SA Pathol, South Australian Clin Genet Serv, Adelaide, SA 5006, AustraliaEric Haan - Womens & Childrens Hosp, SA Pathol, South Australian Clin Genet Serv, Adelaide, SA 5006, AustraliaIsabel Hernandez - Fundació ACEAgustin Ruiz - Fundació ACEMerce Boada - Fundació ACEBarbara Borronils - University of BresciaAlessandro Padovani - University of BresciaCarlos Cruchaga - Washington Univ, Dept Psychiat, St Louis, MO USANigel J. Cairns - Washington Univ, Sch Med, Hope Ctr, St Louis, MO USALuisa Benussi - IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Mol Markers Lab, Brescia, ItalyGiuliano Binetti - IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, MAC Memory Clin, Brescia, ItalyRoberta Ghidoni - IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Mol Markers Lab, Brescia, ItalyGianluigi Forloni - IRCCS Ist Ric Farmacol Mario Negri, Biol Neurodegenerat Disorders, Milan, ItalyDiego Albani - MylanDaniela Galimberti - University of MilanChiara Fenoglio - University of MilanMaria Serpente - University of MilanElio Scarpini - University of MilanJordi Clarim - Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoAlberto Lie - Univ Autonoma Barcelona, Neurol Dept, Memory Unit, Barcelona, SpainRafael Blesa - Univ Autonoma Barcelona, Neurol Dept, Memory Unit, Barcelona, SpainMaria Landqvist Waldo - Lund UniversityKarin Nilsson - Lund UniversityChrister Nilsson - Lund UniversityIan R. A. Mackenzie - University of British ColumbiaGing-Yuek R. Hsiung - University of British ColumbiaDavid M. A. Mann - University of ManchesterJordan Grafman - Northwestern UniversityChristopher M. Morris - Newcastle UniversityJohannes Attems - University of Newcastle AustraliaTimothy D. Griffiths - Newcastle UniversityIan G. McKeith - Newcastle UniversityAlan J. Thomas - Newcastle UniversityPietro Pietrini - IMT Sch Adv Studies, Lucca, Lucca, ItalyEdward D. Huey - Columbia UniversityEric M. Wassermann - NINDS, Behav Neurol Unit, NIH, 10 Ctr DR MSC 1440, Bethesda, MD 20892 USAAtik Baborie - University of AlbertaEvelyn Jaros - Newcastle UniversityMichael C. Tierney - NINDS, Behav Neurol Unit, NIH, 10 Ctr DR MSC 1440, Bethesda, MD 20892 USAPau Pastor - Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, SpainCristina Razquin - Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, Pamplona, SpainSara Ortega-Cubero - Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, SpainElena Alonso - Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, Pamplona, SpainRobert Perneczky - Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Neuroepidemiol & Ageing Res Unit, London W6 8RP, EnglandJanine Diehl-Schmid - Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, GermanyPanagiotis Alexopoulos - Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, GermanyAlexander Kurz - Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, GermanyInnocenzo Rainero - Univ Torino, Dept Neurosci, Neurol 1, Turin, ItalyElisa Rubino - Univ Torino, Dept Neurosci, Neurol 1, Turin, ItalyLorenzo Pinessi - Univ Torino, Dept Neurosci, Neurol 1, Turin, ItalyEkaterina Rogaeva - University of TorontoPeter St George-Hyslop - University of TorontoGiacomina Rossi - Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, I-20133 Milan, ItalyFabrizio Tagliavini - MylanGiorgio Giacconen - Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, I-20133 Milan, ItalyJames B. Rowe - University of CambridgeJohannes C. M. Schlachetzki - Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USAJames Uphill - Massachusetts Rehabilitation CommissionJohn Collinge - Massachusetts Rehabilitation CommissionSimon Mead - Massachusetts Rehabilitation CommissionAdrian Danek - Ludwig Maximilians Univ Munchen, Neurol Klin & Poliklin, Munich, GermanyVivienne M. Van Deerlin - Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USAMurray Grossman - Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USAJohn Q. Trojanowski - Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USAJulie van der Zee - VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, BelgiumMarc Cruts - VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, BelgiumChristine Van Broeckhoven - VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, BelgiumStefano F. Cappa - MylanIsabelle Leber - InsermDidier Hannequin - InsermVeronique Golfier - CH St Brieuc, Serv Neurol, St Brieuc, FranceMartine Vercelletto - Charmo UniversityAlexis Brice - InsermBenedetta Nacmias - University of FlorenceSandro Sorbi - University of FlorenceSilvia Bagnoli - University of FlorenceIrene Piaceri - University of FlorenceJorgen E. Nielsen - Copenhagen Univ Hosp, Rigshosp, Danish Dementia Res Ctr, Dept Neurol,Neurogenet Clin, Copenhagen, DenmarkLena E. Hjermind - Copenhagen Univ Hosp, Rigshosp, Danish Dementia Res Ctr, Dept Neurol,Neurogenet Clin, Copenhagen, DenmarkMatthias Riemenschneider - Saarland UniversityManuel Mayhaus - Saarland UniversityBernd Ibach - University of RegensburgGilles Gasparoni - Saarland UniversitySabrina Pichler - Saarland UniversityWei Gu - Saarland UniversityMartin N. Rossor - UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, Queen Sq, London WC1N 3BG, EnglandNick C. Fox - UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, Queen Sq, London WC1N 3BG, EnglandJason D. Warren - UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Inst Neurol, Queen Sq, London WC1N 3BG, EnglandMaria Grazia Spillantini - University of CambridgeHuw R. Morris - Nashotah House Theological SeminaryPatrizia Rizzu - German Ctr Neurodegenerat Dis Tubingen, Otfried Muellerstr 23, D-72076 Tubingen, GermanyPeter Heutink - German Ctr Neurodegenerat Dis Tubingen, Otfried Muellerstr 23, D-72076 Tubingen, GermanyJulie S. Snowden - University of ManchesterSara Rollinson - University of ManchesterAnna Richardson - University of ManchesterAlexander Gerhard - University of ManchesterAmalie C. Bruni - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyRaffaele Maletta - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyFrancesca Frangipane - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyChiara Cupidi - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyLivia Bernardi - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyMaria Anfossi - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyMaura Gallo - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyMaria Elena Conidi - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyNicoletta Smirne - ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, ItalyRosa Rademakers - Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USAMatt Baker - Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USADennis W. Dickson - Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USANeill R. Graff-Radford - Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USARonald C. Petersen - Mayo Clin Rochester, Dept Neurol, 2001st St SW, Rochester, MN 55904 USADavid Knopman - Mayo Clin Rochester, Dept Neurol, 2001st St SW, Rochester, MN 55904 USAKeith A. Josephs - Mayo Clin Rochester, Dept Neurol, 2001st St SW, Rochester, MN 55904 USABradley F. Boeve - Mayo Clin Rochester, Dept Neurol, 2001st St SW, Rochester, MN 55904 USAJoseph E. Parisi - Mayo Clin Rochester, Dept Pathol, 2001st St SW, Rochester, MN 55904 USAWilliam W. Seeley - Univ Calif San Francisco, Dept Neurol, Box 1207, San Francisco, CA 94143 USABruce L. Miller - Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USAAnna M. Karydas - Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USAHoward Rosen - Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USAJohn C. van Swieten - Erasmus MCElise G. P. Dopper - Erasmus MCHarro Seelaar - Erasmus MCYolande A. L. Pijnenburg - University of AmsterdamPhilip Scheltens - University of AmsterdamGiancarlo Logroscino - University of Bari Aldo MoroRosa Capozzo - University of Bari Aldo MoroValeria Novelli - Fdn Policlin Univ A Gemelli, Med Genet Unit, Rome, ItalyAnnibale A. Puca - MylanMassimo Franceschi - MylanAlfredo Postiglione - University of Naples Federico IIGraziella Milan - ASL Napoli 1 Ctr, Geriatr Ctr Frullone, Naples, ItalyPaolo Sorrentino - ASL Napoli 1 Ctr, Geriatr Ctr Frullone, Naples, ItalyMark Kristiansen - UCL, Inst Child Hlth ICH, UCL Genom, London, EnglandG. Huei-Hsin - Karolinska InstitutetChian Caroline Graff - Karolinska InstitutetFlorence Pasquier - Université de LilleAdeline Rollin - Université de LilleVincent Deramecourt - Université de LilleThibaud Lebouvier - Univ Lille, Inserm 1171, DISTALZ, CHU, F-59000 Lille, FranceLuigi Ferrucci - NIA, Clin Res Branch, Baltimore, MD 21224 USAStuart Pickering-Brown - University of ManchesterAndrew B. Singleton - NIA, Lab Neurogenet, NIH, Bldg 35,Room 1A215,35 Convent Dr, Bethesda, MD 20892 USAJohn Hardy - Nashotah House Theological SeminaryParastoo Momeni - Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lab Neurogenet, 4th St, Lubbock, TX 79430 USAInternational FTD-Genomics Consortium (IFGC)
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.10(1), 12184
- Publisher
- NATURE PORTFOLIO
- DOI
- 10.1038/s41598-020-68848-9
- PMID
- 32699404
- PMCID
- PMC7376149
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Number of pages
- 12
- Grant note
- MC_UU_00024/1; MC_U123160651 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Postdoctoral Science Foundation of Xuzhou Medical University 18YJC910002 / Youth Foundation of Humanity and Social Science - Ministry of Education of China BK20181472 / Natural Science Foundation of Jiangsu; Natural Science Foundation of Jiangsu Province 2014LY112 / Statistical Science Research Project from National Bureau of Statistics of China NF-SI-0617-10175 / National Institute for Health Research; National Institutes of Health Research (NIHR) KC19017 / Social Development Project of Xuzhou 81402765 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) QingLan Research Project of Jiangsu for Outstanding Young Teachers MC_U123160651; G0901254; MR/N026004/1; MC_UU_00024/1; UKDRI-1009; G0701075; G0301152; G0900652; G0502157; G0400074 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 2018M630607; 2019T120465 / China Postdoctoral Science Foundation WSN-087 / Six-Talent Peaks Project in Jiangsu of China
- Language
- English
- Date published
- 07/22/2020
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984627334002771
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