The Institute of Medical Science, Tokai University, Isehara, Kanagawa, Japan.
J Dermatol. 2012 Mar;39(3):231-41. doi: 10.1111/j.1346-8138.2012.01504.x.
During the past 5 years, genome-wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. These studies appeared to provide strong evidence because the susceptibility genes are involved in the interleukin-23/T-helper 17 axis of psoriasis immunopathogenesis and/or skin barrier functions. However, the "identified" genes only explained a small proportion of psoriasis heritability, although it is known to be comparatively higher than that of other common diseases. GWAS are based on the hypothesis that disease-causing variants are high frequency variants within populations. However, this hypothesis is problematic because deleterious variants such as those predisposing to specific diseases will generally not be maintained by selection pressure throughout human evolution. This issue also affects psoriasis studies. Here, we review the current paradigm shift in human genetic analyses and its implications for detection of psoriasis-causing variants based on linkage analysis and GWAS, except the well-known psoriasis susceptibility locus HLA-C.
在过去的 5 年中，全基因组关联研究（GWAS）主要基于单核苷酸多态性标记物，已经确定了许多作为潜在银屑病易感区域的位点。这些研究似乎提供了强有力的证据，因为易感基因参与银屑病免疫发病机制的白细胞介素-23/T 辅助 17 轴和/或皮肤屏障功能。然而，“已确定”的基因仅解释了银屑病遗传率的一小部分，尽管已知其遗传率高于其他常见疾病。GWAS 基于这样的假设，即致病变异是人群中高频变异。然而，这个假设存在问题，因为那些导致特定疾病的有害变异通常不会在人类进化过程中受到选择压力的维持。这个问题也影响到银屑病的研究。在这里，我们回顾了人类遗传分析的当前范式转变及其对基于连锁分析和 GWAS 检测银屑病致病变异的影响，除了众所周知的银屑病易感位点 HLA-C。
