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

Gao, Yixin ; LANDQVIST WALDÖ, MARIA LU ; Nilsson, Karin LU ; Nilsson, Christer LU and Zeng, Ping (2020) In Scientific Reports 10(1).
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... (More)
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. © 2020, The Author(s). (Less)
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
12184
publisher
Nature Publishing Group
external identifiers
  • scopus:85088385622
  • pmid:32699404
ISSN
2045-2322
DOI
10.1038/s41598-020-68848-9
language
English
LU publication?
yes
id
292de28e-8974-48d7-a4f1-6e3913ecad00
date added to LUP
2020-08-04 09:06:42
date last changed
2022-05-04 19:33:25
@article{292de28e-8974-48d7-a4f1-6e3913ecad00,
  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. © 2020, The Author(s).}},
  author       = {{Gao, Yixin and LANDQVIST WALDÖ, MARIA and Nilsson, Karin and Nilsson, Christer and Zeng, Ping}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-68848-9}},
  doi          = {{10.1038/s41598-020-68848-9}},
  volume       = {{10}},
  year         = {{2020}},
}