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

We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genomewide association studies (n= ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n= ~ 23,000 f...

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Detalles Bibliográficos
Autores: Gao, Y. (Yixin)|||/items/63c4d7eb-7e90-4f89-a628-620c1a9cc605, Wang, T. (Ting)|||/items/ba9b74d6-d9e1-48f5-a784-d3cc74ad70f0, Yu, X. (Xinghao)|||/items/7a3ecedb-d560-47ae-8b2e-f24b2a4aff9c, Zhao, H. (Huashuo)|||/items/1c733a23-c632-4f45-a627-642880c3c735, Zeng, P. (Ping)|||/items/c0dc41a3-ec7b-4b80-a5bc-329421778059, Ferrari, R. (Rafaele)|||/items/53ede621-babe-4a63-a562-2408cb4600a2, Hernandez, D.G. (Dena G.)|||/items/25bcab3b-2f59-448a-850c-ee997e149a8c, Nalls, M.A. (Michael A.)|||/items/76e0e289-0e96-4dfd-91fd-e8ae510025d4, Rohrer, J.D. (Jonathan D.)|||/items/77dfa610-c030-4c68-90cd-e6cceca07846, Ramasamy, A. (Adaikalavan)|||/items/142f15ee-0593-4b64-b1d2-e9ff8ef38442, Kwok, J.B.J. (John B. J.)|||/items/7475fe3d-c9dd-4d79-8e3d-b68360616047, Dobson-Stone, C. (Carol)|||/items/b3b0d46a-e32b-4ed2-a221-82e818dcef18, Brooks, W.S. (William S.)|||/items/971dad06-b0bc-4b25-80bf-a8c9591ef6e4, Schofeld, P.R. (Peter R.)|||/items/43c35dba-4ac7-441c-8a60-ae48689b1794, Halliday, G.M. (Glenda M.)|||/items/b533474a-d4ec-40aa-ac25-bc0c0a5d53fe, Hodges, J.R. (John R.)|||/items/8ee061bd-ff27-4050-a514-3f304e5ff650, Piguet, O. (Olivier)|||/items/a3363f8d-22a7-4e34-aa5d-a9b0fd112152, Bartley, L. (Lauren)|||/items/d01a815c-e9ae-4cec-a71d-fe6363e70d16, Thompson, E. (Elizabeth)|||/items/cede5b3b-e299-45f0-90f8-cc915a127d3b, Haan, E. (Eric)|||/items/cd87f222-6ddb-4f53-91b2-f423558654ff, Hernández, I. (Isabel)|||/items/93381e86-e157-4ce0-915d-091d6b0fc338, Ruiz, A. (Agustín)|||/items/36f049d7-924c-4c6c-a9d3-d48ce6924cdf, Boada, M. (Mercè)|||/items/a8a133f9-74bc-441e-b058-00188fc042e2, Borroni, B. (Barbara)|||/items/4d32cecc-d09a-4534-a512-1cf31b9be6f2, Padovani, A. (Alessandro)|||/items/8fbc50c1-1ac0-435d-a985-f5dfc849afaa, Cruchaga, C. (Carlos)|||/items/a08ea75a-3b23-47b7-ba42-4bfc2ab4b5d5, Cairns, N.J. (Nigel J.)|||/items/7f4fa54d-ebe6-459a-b580-873c5fd317d3, Benussi, L. (Luisa)|||/items/0c2e81c5-5eb1-4cc5-9592-97b21a9f330a, Binetti, G. (Giuliano)|||/items/0f8e9934-e3f0-4792-a6c5-6044d050e2e9, Ghidoni, R. (Roberta)|||/items/fca5c854-e0b9-4665-8c8f-3c1e32c20184, Forloni, G. (Gianluigi)|||/items/6bf8d943-9be2-4289-857d-984ea4f6a1a8, Albani, D. (Diego)|||/items/5ba2d5fc-b7a9-4929-b4e4-a9cd4c88bc72, Galimberti, D. (Daniela)|||/items/1e577689-0799-4d94-ad54-39d669a8cb3a, Fenoglio, C. (Chiara)|||/items/cc45c317-abf5-4753-a8d2-9df471139f1b, Serpente, M. (Maria)|||/items/b0e8de19-9c23-407d-ad1f-79db66e60640, Scarpini, E. (Elio)|||/items/24c8c90e-2b9a-45ad-ad64-ee8a64f0672a, Clarimon, J. (Jordi)|||/items/ba53f0fa-1d6e-4e69-b67f-d0ab5646b4c2, Lleó, A. (Alberto)|||/items/0f1c20d5-6414-4289-b8dc-1b33cbc76367, Blesa, R. (Rafael)|||/items/a640023e-ed5a-4a82-b56e-6f760a7e4f3e, Landqvist-Waldö, M. (Maria)|||/items/8cab1d45-7866-4ffe-802f-0c867b3e451c, Nilsson, K. (Karin)|||/items/e1009bb9-f19a-4053-971b-a1fb06fa88ae, Nilsson, C. (Christer)|||/items/b9c2f8c9-127b-43db-864e-e9b73839b732, Mackenzie, I.R.A. 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(Philip)|||/items/2a60bfba-95af-4a29-8eaf-4a0e057255a6, Logroscino, G. (Giancarlo)|||/items/8ca23e8f-e6be-44b3-b4da-c60462376a8a, Capozzo, R. (Rosa)|||/items/06dfa158-2316-4b85-89e3-8c06f3b79767, Novelli, V. (Valeria)|||/items/a6e1038d-fb6b-40f6-ab26-85dbc2f0282c, Puca, A.A. (Annibale A.)|||/items/25eaa9c3-2910-45b4-9a79-b4285c1b9341, Franceschi, M. (Massimo)|||/items/c7b3bae1-1581-4125-9df7-95e145c59e8f, Postiglione, A. (Alfredo)|||/items/b409c0c7-c219-4093-9f39-37c2cf750d1d, Milan, G. (Graziella )|||/items/482a13ce-4d59-4193-90a3-8a11471b389c, Sorrentino, P. (Paolo)|||/items/f0070afa-c55e-4fdc-8b93-a474726b0912, Kristiansen, M. (Mark)|||/items/cb70fff0-834c-45e9-ad53-39b36a5d42fe, Chiang, H.H. (Huei Hsin)|||/items/1c31d11b-6a31-4eca-bd17-c2152124c9f3, Graf, C. (Caroline)|||/items/73c6a0b6-d543-4c42-8333-76fd08bc1e41, Pasquier, F. (Florence)|||/items/8ea3f413-2db8-43a1-8331-77f2054cd4a9, Rollin, A. (Adeline)|||/items/698e7e05-bf13-41f2-ba9f-f8d3f6f619a7, Deramecourt, V. (Vincent)|||/items/bbce95a2-048d-4987-b600-9675cbcf5afe, Lebouvier, T. (Thibaud)|||/items/607b06ea-48d9-4c33-b2b2-8586744398e9, Kapogiannis, D. (Dimitrios)|||/items/3ce45ab3-cdef-4231-ac41-ba5d6bb56850, Ferrucci, L. (Luigi)|||/items/cf64e274-5482-4422-a217-c3039eae9b52, Pickering-Brown, S. (Stuart)|||/items/cf53cb2c-36f8-4185-bd99-c4b59074da05, Singleton, A.B. (Andrew B.)|||/items/3ba23187-007d-49cd-b314-e526152b63b0, Hardy, J. (John)|||/items/3e49c7d1-1fd5-45e4-b4f0-c6091476b8d6, Momeni, P. (Parastoo)|||/items/d8918676-dc11-41aa-a14a-2dce01d84a8a
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/66741
Acceso en línea:https://hdl.handle.net/10171/66741
Access Level:acceso abierto
Palabra clave:Computational biology and bioinformatics
Medical research
Neurology
Genetics
Risk factors
Descripción
Sumario:We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genomewide 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 efect 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 infuence of LTL and ALS in the European population.

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