2012年10月26日 讯 /生物谷BIOON/ --在一项新的研究中，包括来自加拿大西蒙弗雷泽大学的两位研究人员在内的5名科学家发现我们30%多发性硬化症(Multiple Sclerosis, MS)遗传易感性能够用我们基因组上的475806个基因变异体来解释。全基因组关联分析(Genome-wide Association Studies, GWAS)常被用来筛选这些变异体，以便寻求疾病的基因关联性。西蒙弗雷泽大学生物学博士研究生Corey Watson和他的导师Felix Breden与来自英国的三名科学家最近他们的研究结果刊登在Scientific Reports期刊上。
多发性硬化症是一种中枢神经系统的炎性疾病，也是年轻人中最为常见的神经疾病。
Watson和他的同事们密切地研究了在1845名多发性硬化症病人体内利用全基因组关联分析鉴定出的主要组织相容性复合体(major histocompatibility complex, MHC)变异体，并协助量化多发性硬化症的遗传易感性。MHC区域长期以来就与多发性硬化症易感性相关联。他们还把这些多发性硬化症病人的MHC变异体和5164名没有患有多发性硬化症的对照者的那些变异体进行比较。
他们注意到我们30%的多发性硬化症遗传易感性中的8%与第六号染色体上的小DNA片段变异相关联，而且这些小DNA片段变异长期以来也与多发性硬化症易感性相关联。
MHC编码促进免疫系统中某些细胞之间的通信的蛋白。在基因组中MHC区域之外，大量的遗传易感性还没有被确定，这是因为当前研究不允许捕捉到我们基因组上的所有变异体。
研究人员认为用来寻求多发性硬化症的其他基因病因的一个位置可能位于人群中拥有罕见变异体的基因内。Watson注意到，“最近的两项研究已解释了罕见基因变异体在多发性硬化症中的重要性，但是这些变异体也通常很难利用全基因组关联分析捕捉到的基因标记来加以描述。”(生物谷Bioon.com)
doi: 10.1038/srep00770
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Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs
Corey T. Watson, Giulio Disanto, Felix Breden, Gavin Giovannoni & Sreeram V. Ramagopalan
Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.
