研究分析了47429例MS和68374例对照受试者的遗传数据，并建立了MS遗传结构的参考图谱，其中包括主要组织相容性复合体（MHC）之外的200个常染色体易感性变体、一个X染色体变体以及32个拓展的MHC基因变体。研究人员使用了多种方法来对551种可能的易感基因进行优先排序，这些基因提示了分布在免疫系统细胞成分中的多个先天和适应性途径。

使用分选的人类小胶质细胞的表达谱，研究人员观察到了这些脑驻留免疫细胞中MS基因的富集，表明这些基因可能在靶向中枢神经系统自身免疫过程中发挥作用，尽管MS最有可能最初是由周围免疫反应的扰动所触发的。

附：英文原文

Title: Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author: International Multiple Sclerosis Genetics Consortium*

Issue&Volume: Volume 365 Issue 6460

Abstract:

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

DOI: 10.1126/science.aav7188

Source: https://science.sciencemag.org/content/365/6460/eaav7188