Department of Biostatistics and Health Informatics, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
Sci Rep. 2022 Jul 22;12(1):12586. doi: 10.1038/s41598-022-16772-5.
Amyotrophic lateral sclerosis (ALS) is a devastating, heterogeneous neurodegenerative neuromuscular disease that leads to a fatal outcome within 2-5 years, and yet, a precise nature of the association between its major phenotypes and the cerebellar role in ALS pathology remains unknown. Recently, repeat expansions in several genes in which variants appreciably contribute to cerebellar pathology, including C9orf72, NIPA1, ATXN2 and ATXN1, have been found to confer a significant risk for ALS. To better define this relationship, we performed MAGMA gene-based analysis and tissue enrichment analysis using genome-wide association study summary statistics based on a study of 27,205 people with ALS and 110,881 controls. Our preliminary results imply a striking cerebellar tissue specificity and further support increasing calls for re-evaluation of the cerebellar role in the ALS pathology.
肌萎缩侧索硬化症（ALS）是一种破坏性的、异质性的神经退行性神经肌肉疾病，导致 2-5 年内致命，但其主要表型与小脑在 ALS 病理中的作用之间的确切关联仍不清楚。最近，在几个基因中发现了重复扩展，其中变体明显有助于小脑病理，包括 C9orf72、NIPA1、ATXN2 和 ATXN1，这些基因显著增加了 ALS 的风险。为了更好地定义这种关系，我们使用 MAGMA 基于基因的分析和组织富集分析，使用基于对 27205 名 ALS 患者和 110881 名对照的全基因组关联研究汇总统计数据。我们的初步结果表明小脑组织具有显著的特异性，并进一步支持了重新评估小脑在 ALS 病理中的作用的呼声。
