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Neurobiol Aging. 2018 Jul;67:202.e1-202.e6. doi: 10.1016/j.neurobiolaging.2018.03.022. Epub 2018 Mar 27.

Polygenic link between blood lipids and amyotrophic lateral sclerosis.

Author information

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address: xu.chen@ki.se.
2
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
3
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

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.

KEYWORDS:

Amyotrophic lateral sclerosis; Blood lipids; Genome-wide association studies; Mendelian randomization study; Polygenic risk score

[Indexed for MEDLINE]

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