The genetics of multiple sclerosis: an up-to-date review.
The genetics of multiple sclerosis: an up-to-date review.
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DOI：
10.1111/j.1600-065x.2012.01134.x
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发表时间：
2012-07
影响因子：
8.7
通讯作者：
Baranzini SE
中科院分区：
文献类型：
--
作者：
Gourraud PA;Harbo HF;Hauser SL;Baranzini SE
多发性硬化症(MS)是一种常见的中枢神经系统炎症性疾病，通常会导致年轻人的残疾。治疗选择有限，而且往往只有部分有效。这种疾病很可能是由多个基因和环境因素之间的复杂相互作用引起的，导致炎症介导的中枢神经系统恶化。一系列基因组研究证实了免疫系统在多发性硬化症发病中的核心作用，包括遗传关联研究，这些研究现已极大地扩大了多发性硬化症易感基因的花名册，超过了近40年前首次发现的多发性硬化症的长期关联。技术的进步和跨研究小组协作的新模式已经使50多个与MS相关的非人类白细胞抗原遗传风险因素得以发现。然而，由于很大一部分疾病的遗传性仍未得到解释，目前的研究重点是鉴定因果等位基因、相关的途径、表观遗传机制和基因-环境相互作用。这篇文章将回顾最近在解决多发性硬化症遗传学方面的努力，以及不断增加的可分析数据带来的挑战，这是应对这种复杂性所必需的新统计方法的先锋发展。
Multiple sclerosis (MS) is a prevalent inflammatory disease of the central nervous system that often leads to disability in young adults. Treatment options are limited and often only partly effective. The disease is likely caused by a complex interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration. A series of genomic studies have confirmed a central role for the immune system in the development of MS, including genetic association studies which have now dramatically expanded the roster of MS susceptibility genes beyond the longstanding HLA association in MS first identified nearly 40 years ago. Advances in technology together with novel models for collaborative across research groups have enabled the discovery of more than 50 non-HLA genetic risk factors associated with MS. However, with a large proportion of the disease heritability still unaccounted for, current studies are now geared towards identification of causal alleles, associated pathways, epigenetic mechanisms, and gene-environment interactions. This article will review recent efforts in addressing the genetics of MS and the challenges posed by an ever increasing amount of analyzable data which is spearheading development of novel statistical methods necessary to cope with such complexity.