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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 genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,00...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376149/ https://www.ncbi.nlm.nih.gov/pubmed/32699404 http://dx.doi.org/10.1038/s41598-020-68848-9 |
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author | Gao, Yixin Wang, Ting Yu, Xinghao Zhao, Huashuo Zeng, Ping |
author_facet | Gao, Yixin Wang, Ting Yu, Xinghao Zhao, Huashuo Zeng, Ping |
author_sort | Gao, Yixin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7376149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73761492020-07-24 Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis Gao, Yixin Wang, Ting Yu, Xinghao Zhao, Huashuo Zeng, Ping Sci Rep Article 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. Nature Publishing Group UK 2020-07-22 /pmc/articles/PMC7376149/ /pubmed/32699404 http://dx.doi.org/10.1038/s41598-020-68848-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gao, Yixin Wang, Ting Yu, Xinghao Zhao, Huashuo Zeng, Ping Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title | Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title_full | Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title_fullStr | Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title_full_unstemmed | Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title_short | Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
title_sort | mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376149/ https://www.ncbi.nlm.nih.gov/pubmed/32699404 http://dx.doi.org/10.1038/s41598-020-68848-9 |
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