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@ARTICLE{Xia:258246,
author = {Xia, Kailin and Klose, Veronika and Högel, Josef and
Huang, Tao and Zhang, Linjing and Dorst, Johannes and Fan,
Dongsheng and Ludolph, Albert C},
title = {{L}ipids and amyotrophic lateral sclerosis: {A} two-sample
{M}endelian randomization study.},
journal = {European journal of neurology},
volume = {30},
number = {7},
issn = {1351-5101},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2023-00592},
pages = {1899 - 1906},
year = {2023},
abstract = {Previous observational studies revealed a potential but
partially controversial relation between lipid metabolism
and the risk of amyotrophic lateral sclerosis (ALS),
potentially prone to bias. Therefore, we aimed to study
whether lipid metabolism involves genetically determined
risk factors for ALS through Mendelian randomization (MR)
analysis.Using genome-wide association study summary-level
data for total cholesterol (TC) (n = 188,578), high-density
lipoprotein cholesterol (HDL-C) (n = 403,943), low-density
lipoprotein cholesterol (LDL-C) (n = 440,546),
apolipoprotein A1 (ApoA1) (n = 391,193), apolipoprotein B
(ApoB) (n = 439,214), and ALS (12,577 cases and 23,475
controls), we implemented a bidirectional MR study to
evaluate a genetic relation between lipids and ALS risk. We
performed a mediation analysis to assess whether LDL-C is a
potential mediator on the pathway from traits of
LDL-C-related polyunsaturated fatty acids (PUFAs) to ALS
risk.We identified genetically predicted increased lipid
levels to be associated with the risk of ALS, whereby
elevated LDL-C had the most potent effect (OR 1.028, $95\%$
CI 1.008-1.049, p = 0.006). The effect of increased levels
of apolipoproteins on ALS was similar to their corresponding
lipoproteins. ALS did not cause any changes in lipid levels.
We found no relation between LDL-C-modifying lifestyles and
ALS. The mediation analysis revealed that LDL-C could act as
an active mediator for linoleic acid, with the mediation
effect estimated to be 0.009.We provided high-level genetic
evidence verifying the positive link between preclinically
elevated lipid and ALS risk that had been described in
previous genetic and observational studies. We also
demonstrated the mediating role of LDL-C in the pathway from
PUFAs to ALS.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: epidemiology /
Amyotrophic Lateral Sclerosis: genetics / Cholesterol, LDL:
genetics / Mendelian Randomization Analysis / Genome-Wide
Association Study / Risk Factors / Polymorphism, Single
Nucleotide / Triglycerides: genetics / Mendelian
randomization (Other) / amyotrophic lateral sclerosis
(Other) / genetics (Other) / instrumental variables (Other)
/ lipids (Other) / Cholesterol, LDL (NLM Chemicals) /
Triglycerides (NLM Chemicals)},
cin = {Clinical Study Center Ulm / AG Zhan},
ddc = {610},
cid = {I:(DE-2719)5000077 / I:(DE-2719)1910005},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 354 -
Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36999624},
doi = {10.1111/ene.15810},
url = {https://pub.dzne.de/record/258246},
}