Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Neurobiol Aging. 2018 Jul;67:202.e1-202.e6. doi: 10.1016/j.neurobiolaging.2018.03.022. Epub 2018 Mar 27.
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.
血脂异常在肌萎缩侧索硬化症（ALS）患者中很常见。我们旨在通过对全基因组关联研究汇总结果的多基因分析来检验血脂与 ALS 之间的关联和因果关系。基于低密度脂蛋白胆固醇（LDL-C）和总胆固醇（TC）风险等位基因的多基因风险评分（PRS）与 ALS 风险的增加显著相关。使用与 LDL-C 和 TC 特异性相关的单核苷酸多态性（SNP）作为工具变量，在 Mendelian 随机化分析中鉴定出 LDL-C 和 TC 对 ALS 风险的统计学显著因果效应。基于甘油三酯或高密度脂蛋白胆固醇风险等位基因的 PRS 与 ALS 之间无显著相关性，并且基于 ALS 风险等位基因的 PRS 与任何研究的脂质均无相关性。这项研究支持高水平的 LDL-C 和 TC 是 ALS 的危险因素，并且还表明 LDL-C 和 TC 与 ALS 之间存在因果关系。
