1. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- Author
-
Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), Zeng, P. (Ping), Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), and Zeng, P. (Ping)
- 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.
- Published
- 2020
- Full Text
- View/download PDF