小柯机器人

近日，国际多发性硬化症遗传学联盟发现，严重性位点牵涉到多发性硬化症进展中的中枢神经系统复原力。2023年6月28日，《自然》杂志在线发表了这项成果。

为了深入了解参与进展的潜在机制，研究人员对12584例年龄相关的多发性硬化症（MS）严重程度评分进行了全基因组关联研究，并在另外9805例中重现了这些发现。研究人员发现与DYSF-ZNF638位点的rs10191329有显著关联，其风险等位基因与同型携带者需要步行辅助工具的时间中位数缩短3.7年有关，并与脑干和脑组织中皮质病理学的增加有关。

研究人员还发现与DNM3-PIGC基因座的rs149097173有提示性的关联，并且在中枢神经系统（CNS）组织中有明显的遗传性富集。孟德尔随机化分析表明，较高的教育程度有潜在的保护作用。与免疫驱动的易感性相比，这些发现表明CNS的复原力和潜在的神经认知储备在决定MS的结果中起着关键作用。

据悉，MS是一种CNS的自身免疫性疾病，在大多数患者中会导致显著的神经变性，是年轻成人慢性神经系统残疾的常见原因。

附：英文原文

Title: Locus for severity implicates CNS resilience in progression of multiple sclerosis

Author: anonymous

Issue&Volume: 2023-06-28

Abstract: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults1,2. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF–ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3–PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility3, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.

DOI: 10.1038/s41586-023-06250-x

Source: https://www.nature.com/articles/s41586-023-06250-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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