Baranzini Sergio E, Oksenberg Jorge R
Weill Institute for Neurosciences. Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA; Graduate Program in Bioinformatics, University of California San Francisco, San Francisco, CA, USA.
Weill Institute for Neurosciences. Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
Trends Genet. 2017 Dec;33(12):960-970. doi: 10.1016/j.tig.2017.09.004. Epub 2017 Oct 5.
Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. Here, we present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes.
多发性硬化症（MS）是一种常见的自身免疫性疾病，其攻击目标是中枢神经系统（CNS）中的髓鞘。在过去10年里，多项全基因组关联研究（GWAS）已经发现了200多个独立促成疾病发病机制的基因座。与许多其他复杂疾病一样，患MS的风险是由多个常见变异驱动的，这些变异的生物学效应并不立即明确。在此，我们对MS遗传学所取得的进展进行历史回顾，并讨论当前为创建一个更完整模型所做的工作，该模型要能准确呈现MS易感性的遗传图谱。这样一个模型必然包括对每个常见变异对细胞表型的个体贡献以及与其他基因和环境的相互作用有更好的理解。MS未来的遗传学研究可能会聚焦于罕见变异和内表型的作用。
