Kumar Vinod, Wijmenga Cisca, Xavier Ramnik J
University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.
University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.
Curr Opin Immunol. 2014 Dec;31:51-7. doi: 10.1016/j.coi.2014.09.007. Epub 2014 Oct 14.
Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents. We propose that the interdisciplinary studies (genetics-genomics-immunology-infection-bioinformatics) are the future post-GWAS approaches to advance our understanding of the pathogenesis of immune-mediated diseases.
基因关联研究不仅确定了数百个免疫介导疾病的易感基因座，还查明了HLA基因中导致许多自身免疫反应的因果氨基酸变体。大多数非HLA基因变体位于非编码调控区域。表达定量性状位点研究表明，这些变体主要通过调节基因表达来影响疾病。我们讨论了感染性疾病和免疫介导疾病之间共享基因座的最新研究结果，并提供了在这些感染因子背景下探索基因关联的潜在线索。我们提出，跨学科研究（遗传学-基因组学-免疫学-感染-生物信息学）是全基因组关联研究（GWAS）之后推进我们对免疫介导疾病发病机制理解的未来研究方法。
