期刊
NEUROBIOLOGY OF AGING
卷 67, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2018.03.022
关键词
Blood lipids; Amyotrophic lateral sclerosis; Genome-wide association studies; Polygenic risk score; Mendelian randomization study
资金
- Swedish Research Council [2015-03170]
- Karolinska Institutet
- Ulla-Carin Lindquist Foundation
- China Scholarship Council [201306210065]
- Swedish Research Council [2015-03170] Funding Source: Swedish Research Council
- Vinnova [2015-03170] Funding Source: Vinnova
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. (C) 2018 Elsevier Inc. All rights reserved.
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