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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis. / Gao, Yixin; Wang, Ting; Yu, Xinghao; Ferrari, Raffaele; Hernandez, Dena G.; Nalls, Michael A.; Rohrer, Jonathan D.; Ramasamy, Adaikalavan; Kwok, John B.J.; Dobson-Stone, Carol; Brooks, William S.; Schofield, Peter R.; Halliday, Glenda M.; Hodges, John R.; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J.; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Albani, Diego; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R.A.; Hsiung, Ging Yuek R.; Mann, David M.A.; Grafman, Jordan; Morris, Christopher M.; Attems, Johannes; Griffiths, Timothy D.; Rowe, James B.; Nielsen, Jørgen E.; Hjermind, Lena E.; International FTD-Genomics Consortium (IFGC).

I: Scientific Reports, Bind 10, Nr. 1, 12184, 2020.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Gao, Y, Wang, T, Yu, X, Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks, WS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, Rowe, JB, Nielsen, JE, Hjermind, LE & International FTD-Genomics Consortium (IFGC) 2020, 'Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis', Scientific Reports, bind 10, nr. 1, 12184. https://doi.org/10.1038/s41598-020-68848-9

APA

Gao, Y., Wang, T., Yu, X., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Brooks, W. S., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, I., ... International FTD-Genomics Consortium (IFGC) (2020). Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis. Scientific Reports, 10(1), [12184]. https://doi.org/10.1038/s41598-020-68848-9

Vancouver

Gao Y, Wang T, Yu X, Ferrari R, Hernandez DG, Nalls MA o.a. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis. Scientific Reports. 2020;10(1). 12184. https://doi.org/10.1038/s41598-020-68848-9

Author

Gao, Yixin ; Wang, Ting ; Yu, Xinghao ; Ferrari, Raffaele ; Hernandez, Dena G. ; Nalls, Michael A. ; Rohrer, Jonathan D. ; Ramasamy, Adaikalavan ; Kwok, John B.J. ; Dobson-Stone, Carol ; Brooks, William S. ; Schofield, Peter R. ; Halliday, Glenda M. ; Hodges, John R. ; Piguet, Olivier ; Bartley, Lauren ; Thompson, Elizabeth ; Haan, Eric ; Hernández, Isabel ; Ruiz, Agustín ; Boada, Mercè ; Borroni, Barbara ; Padovani, Alessandro ; Cruchaga, Carlos ; Cairns, Nigel J. ; Benussi, Luisa ; Binetti, Giuliano ; Ghidoni, Roberta ; Forloni, Gianluigi ; Albani, Diego ; Galimberti, Daniela ; Fenoglio, Chiara ; Serpente, Maria ; Scarpini, Elio ; Clarimón, Jordi ; Lleó, Alberto ; Blesa, Rafael ; Waldö, Maria Landqvist ; Nilsson, Karin ; Nilsson, Christer ; Mackenzie, Ian R.A. ; Hsiung, Ging Yuek R. ; Mann, David M.A. ; Grafman, Jordan ; Morris, Christopher M. ; Attems, Johannes ; Griffiths, Timothy D. ; Rowe, James B. ; Nielsen, Jørgen E. ; Hjermind, Lena E. ; International FTD-Genomics Consortium (IFGC). / Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis. I: Scientific Reports. 2020 ; Bind 10, Nr. 1.

Bibtex

@article{2e9b8da09b7946e381989e7e3f271b3c,
title = "Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis",
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.",
author = "Yixin Gao and Ting Wang and Xinghao Yu and Raffaele Ferrari and Hernandez, {Dena G.} and Nalls, {Michael A.} and Rohrer, {Jonathan D.} and Adaikalavan Ramasamy and Kwok, {John B.J.} and Carol Dobson-Stone and Brooks, {William S.} and Schofield, {Peter R.} and Halliday, {Glenda M.} and Hodges, {John R.} and Olivier Piguet and Lauren Bartley and Elizabeth Thompson and Eric Haan and Isabel Hern{\'a}ndez and Agust{\'i}n Ruiz and Merc{\`e} Boada and Barbara Borroni and Alessandro Padovani and Carlos Cruchaga and Cairns, {Nigel J.} and Luisa Benussi and Giuliano Binetti and Roberta Ghidoni and Gianluigi Forloni and Diego Albani and Daniela Galimberti and Chiara Fenoglio and Maria Serpente and Elio Scarpini and Jordi Clarim{\'o}n and Alberto Lle{\'o} and Rafael Blesa and Wald{\"o}, {Maria Landqvist} and Karin Nilsson and Christer Nilsson and Mackenzie, {Ian R.A.} and Hsiung, {Ging Yuek R.} and Mann, {David M.A.} and Jordan Grafman and Morris, {Christopher M.} and Johannes Attems and Griffiths, {Timothy D.} and Rowe, {James B.} and Nielsen, {J{\o}rgen E.} and Hjermind, {Lena E.} and {International FTD-Genomics Consortium (IFGC)}",
year = "2020",
doi = "10.1038/s41598-020-68848-9",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

AU - Gao, Yixin

AU - Wang, Ting

AU - Yu, Xinghao

AU - Ferrari, Raffaele

AU - Hernandez, Dena G.

AU - Nalls, Michael A.

AU - Rohrer, Jonathan D.

AU - Ramasamy, Adaikalavan

AU - Kwok, John B.J.

AU - Dobson-Stone, Carol

AU - Brooks, William S.

AU - Schofield, Peter R.

AU - Halliday, Glenda M.

AU - Hodges, John R.

AU - Piguet, Olivier

AU - Bartley, Lauren

AU - Thompson, Elizabeth

AU - Haan, Eric

AU - Hernández, Isabel

AU - Ruiz, Agustín

AU - Boada, Mercè

AU - Borroni, Barbara

AU - Padovani, Alessandro

AU - Cruchaga, Carlos

AU - Cairns, Nigel J.

AU - Benussi, Luisa

AU - Binetti, Giuliano

AU - Ghidoni, Roberta

AU - Forloni, Gianluigi

AU - Albani, Diego

AU - Galimberti, Daniela

AU - Fenoglio, Chiara

AU - Serpente, Maria

AU - Scarpini, Elio

AU - Clarimón, Jordi

AU - Lleó, Alberto

AU - Blesa, Rafael

AU - Waldö, Maria Landqvist

AU - Nilsson, Karin

AU - Nilsson, Christer

AU - Mackenzie, Ian R.A.

AU - Hsiung, Ging Yuek R.

AU - Mann, David M.A.

AU - Grafman, Jordan

AU - Morris, Christopher M.

AU - Attems, Johannes

AU - Griffiths, Timothy D.

AU - Rowe, James B.

AU - Nielsen, Jørgen E.

AU - Hjermind, Lena E.

AU - International FTD-Genomics Consortium (IFGC)

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-68848-9

DO - 10.1038/s41598-020-68848-9

M3 - Journal article

C2 - 32699404

AN - SCOPUS:85088385622

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12184

ER -

ID: 247500593