Polygenic link between blood lipids and amyotrophic lateral sclerosis
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Abstract
Dyslipidemia is common among patients with amyotrophic lateral sclerosis (ALS). We aimed to test the association and causality between blood lipids and ALS, using polygenic analyses on the summary results of genome-wide association studies. Polygenic risk scores (PRSs) based on low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) risk alleles were significantly associated with a higher risk of ALS. Using single nucleotide polymorphisms (SNPs) specifically associated with LDL-C and TC as the instrumental variables, statistically significant causal effects of LDL-C and TC on ALS risk were identified in Mendelian randomization analysis. No significant association was noted between PRSs based on triglycerides or high-density lipoprotein cholesterol risk alleles and ALS, and the PRSs based on ALS risk alleles were not associated with any studied lipids. This study supports that high levels of LDL-C and TC are risk factors for ALS, and it also suggests a causal relationship of LDL-C and TC to ALS.
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Mendelian randomization studies suggest a causal positive association between total cholesterol and low-density lipoprotein (LDL) and ALS risk.
“The association observed for a history of hypercholesterolemia and a higher risk of ALS in this study is consistent with Mendelian randomization studies suggesting a causal positive association between total cholesterol and low-density lipoprotein (LDL) and ALS risk [30, 31] as well as with observational studies indicating a higher level of total cholesterol among ALS cases than controls [32].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [31]
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Sewell-Green, A. R., Kuiper, M. M., Holdom, C. J., Beelen, A., Ngo, S. T., Steyn, F. J., & Matthews-Rensch, K. L. (2025) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2025.2574685
- Authors
- Chen, X., Yazdani, S., Piehl, F., Magnusson, P. K. E., & Fang, F.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Chen, Xu
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 67
- Pages
- 202.e1-202.e6
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2952379127
- Cited by
- 63
- References
- 19
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 7 · 2018: 2
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Swedish Research Council (2015-03170)
- Karolinska Institutet
- China Scholarship Council (201306210065)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- amyotrophic lateral sclerosis, serum lipids, dyslipidemia, LDL cholesterol, total cholesterol, polygenic risk score, Mendelian randomization, causal effects, triglycerides, HDL cholesterol, genetic risk factors
- MeSH terms
- Alleles, Amyotrophic Lateral Sclerosis, Humans, Cholesterol, HDL, Cholesterol, LDL, Risk, Triglycerides, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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