Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Curr Opin Immunol. 2012 Oct;24(5):544-51. doi: 10.1016/j.coi.2012.09.002. Epub 2012 Oct 3.
There has been considerable progress in our understanding of the genetic architecture of susceptibility to inflammatory diseases in recent years: several hundred susceptibility loci have been discovered in genome-wide association studies (GWAS) of human populations. This success has created an important challenge in identifying the functional consequences of these risk-associated variants and in elucidating how the repercussions of individual susceptibility loci integrate to yield dysregulation of immune pathways and, ultimately, syndromic clinical phenotypes. The integration of GWAS association signals with high-resolution transcriptome and other genomic data that capture the dynamics of cellular state and function in the context of individual's collection of susceptibility alleles has proven to be a successful avenue of investigation. The rapid pace of methodological development in this area has been coupled with an accumulation of experimental data that makes the elucidation of complex biological networks underlying susceptibility to these common inflammatory diseases a reasonable goal in the near future.
近年来，我们对炎症性疾病易感性的遗传结构有了相当大的了解：在人类群体的全基因组关联研究（GWAS）中发现了数百个易感位点。这一成功为识别这些风险相关变体的功能后果以及阐明个体易感性位点的影响如何整合以导致免疫途径失调，并最终导致综合征临床表型带来了重要挑战。将 GWAS 关联信号与高分辨率转录组和其他基因组数据相结合，这些数据可以捕获个体易感等位基因集合背景下细胞状态和功能的动态，已被证明是一种成功的研究途径。该领域方法学发展的快速步伐伴随着实验数据的积累，使得阐明这些常见炎症性疾病易感性背后的复杂生物学网络成为近期内一个合理的目标。
