Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Mol Neurobiol. 2015 Feb;51(1):361-9. doi: 10.1007/s12035-014-8673-1. Epub 2014 Mar 20.
Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disease after Alzheimer's disease (AD) and Parkinson's disease (PD). In order to unravel more genetic etiology of ALS, genome-wide association studies (GWAS) have been conducted. However, the newly identified ALS susceptibility loci exert only very small risk effects and cannot fully explain the underlying ALS genetic risk. A large proportion of the heritability of ALS is still to be explained. Recently, pathway analysis of GWAS has been used to investigate the mechanisms of AD and PD. We think that AD or PD risk pathways may also be involved in ALS. In order to confirm this view, we conducted a pathway analysis of two independent ALS GWAS. We identified multiple classifications of the Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism, immune system and diseases, environmental information processing, genetic information processing, cellular processes, and nervous system and neurodegenerative diseases to be the consistent signals in the two ALS GWAS. On the single pathway level, we identified 12 shared pathways. We compared the findings from ALS GWAS with those of previous pathway analyses of AD and PD GWAS. The results further supported the involvement of AD and PD risk pathways in ALS. We believe that our results may advance the understanding of ALS mechanisms and will be very useful for future genetic studies.
肌萎缩侧索硬化症（ALS）是继阿尔茨海默病（AD）和帕金森病（PD）之后的第三大常见神经退行性疾病。为了揭示更多的 ALS 遗传病因，已经进行了全基因组关联研究（GWAS）。然而，新发现的 ALS 易感性位点仅产生很小的风险效应，不能完全解释潜在的 ALS 遗传风险。ALS 的大部分遗传率仍有待解释。最近，GWAS 的途径分析已被用于研究 AD 和 PD 的机制。我们认为 AD 或 PD 的风险途径也可能与 ALS 有关。为了证实这一观点，我们对两项独立的 ALS GWAS 进行了途径分析。我们确定了与代谢、免疫系统和疾病、环境信息处理、遗传信息处理、细胞过程以及神经系统和神经退行性疾病相关的京都基因和基因组百科全书途径的多个分类，这些分类是两个 ALS GWAS 中的一致信号。在单个途径水平上，我们确定了 12 个共享途径。我们将 ALS GWAS 的发现与 AD 和 PD GWAS 的先前途径分析进行了比较。结果进一步支持 AD 和 PD 风险途径参与 ALS。我们相信，我们的研究结果可能有助于深入了解 ALS 的发病机制，并将对未来的遗传研究非常有用。
