多发性硬化是一种中枢神经系统疾病，涉及炎症与神经退化之间的相互作用。尽管人们对此进行了很多研究，但决定这种疾病易感性的遗传架构仍未确定。一项涉及近1万人（全部为欧洲裔）的全基因组关联的研究项目，证实了以前报告过的与多发性硬化相关的DNA区域，并识别出另外29个新的易感性位点。进一步的分析表明，T-helper细胞的分化与这种疾病的发病机理紧密相关。
生物探索推荐英文摘要
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple
