Department of Neurology, University of California-San Francisco, San Francisco, CA, USA.
Mult Scler. 2018 Jan;24(1):75-79. doi: 10.1177/1352458517737371.
A broad scientific consensus has emerged linking multiple sclerosis (MS) risk to multiple independent and interacting DNA variants that are relatively frequent in the population and act in concert with environmental exposures. The multifactorial, polygenic model of heritability provided the rationale and impetus to pursue genome-wide association studies (GWAS), which have been highly successful in uncovering genetic variants influencing susceptibility. Over 200 loci have been firmly associated with MS susceptibility. The main association signal genome-wide maps to the major histocompatibility complex ( MHC) gene cluster in chromosome 6p21. This association has been observed across all populations studied. However, a significant proportion of MS heritability remains unexplained. Decoding the genetics of MS represents a long-standing and important research goal in this disease, as the demonstration of even modest functional genomic effects on risk or the course of MS is likely to reveal fundamental disease mechanisms and possibly yield new therapeutic opportunities.
已经出现了广泛的科学共识，将多发性硬化症（MS）风险与人群中相对常见的多个独立且相互作用的 DNA 变体联系起来，这些变体与环境暴露协同作用。多因素、多基因遗传模型为全基因组关联研究（GWAS）提供了理论依据和动力，GWAS 在发现影响易感性的遗传变异方面非常成功。已有 200 多个位点与 MS 易感性密切相关。全基因组范围内的主要关联信号映射到染色体 6p21 上的主要组织相容性复合体（MHC）基因簇。这种关联在所有研究的人群中都观察到了。然而，MS 遗传率的很大一部分仍然无法解释。解析 MS 的遗传学是该疾病的一个长期而重要的研究目标，因为即使对 MS 风险或病程的功能基因组影响很小的证明，也可能揭示基本的疾病机制，并可能带来新的治疗机会。
