Primary Immunodeficiencies and Inflammatory Disease: A Growing Genetic Intersection.
Primary Immunodeficiencies and Inflammatory Disease: A Growing Genetic Intersection.
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DOI：
10.1016/j.it.2015.12.006
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发表时间：
2016-02
影响因子：
16.8
通讯作者：
Gros P
中科院分区：
文献类型：
--
作者：
Fodil N;Langlais D;Gros P
基因组分析的最新进展为感染性和炎症性疾病的遗传结构提供了重要的见解。通过全基因组关联研究（GWAS）在22种炎症性疾病中检测到的基因座的组合分析揭示了在病理性炎症中发挥核心作用的共享遗传核心和相关生化途径。平行的全外显子组测序研究已经确定了265个原发性免疫缺陷（PID）基因突变。在这里，我们研究了这两个数据集之间的重叠，发现它由保护免受感染所必需的基因组成，并且持续激活会导致病理性炎症。基于这种交叉，我们提出，虽然这些基因中的强突变或失活突变（罕见变异）可能导致严重疾病（PID），但它们可能通过常见的调控/编码变异进行更微妙的调节，可能导致慢性炎症。
Recent advances in genome analysis have provided important insights into the genetic architecture of infectious and inflammatory diseases. The combined analysis of loci detected by genome-wide association studies (GWAS) in 22 inflammatory diseases has revealed a shared genetic core and associated biochemical pathways that play a central role in pathological inflammation. Parallel whole exome sequencing studies have identified 265 genes mutated in primary immunodeficiencies (PID). Here we examine the overlap between these two datasets, and find that it consists of genes essential for protection against infections and in which persistent activation causes pathological inflammation. Based on this intersection, we propose that although strong or inactivating mutations (rare variants) in these genes may cause severe disease (PIDs), their more subtle modulation potentially by common regulatory/coding variants may contribute to chronic inflammation.