Department of Biostatistics, Yale School of Public Health New Haven, CT, USA.
Front Genet. 2013 Dec 9;4:280. doi: 10.3389/fgene.2013.00280.
In the recent decade, high-throughput genotyping and next-generation sequencing platforms have enabled genome-wide association studies (GWAS) of many complex human diseases. These studies have discovered many disease susceptible loci, and unveiled unexpected disease mechanisms. Despite these successes, these identified variants only explain a small proportion of the genetic contributions to these diseases and many more remain to be found. This is largely due to the small effect sizes of most disease-associated variants and limited sample size. As a result, it is critical to leverage other information to more effectively prioritize GWAS signals to increase replication rates and better understand disease mechanisms. In this review, we introduce the biological/genomic features that have been found to be informative for post-GWAS prioritization, and discuss available tools to utilize these features for prioritization.
在最近的十年中,高通量基因分型和下一代测序平台使全基因组关联研究(GWAS)能够应用于许多复杂的人类疾病。这些研究发现了许多疾病易感基因座,并揭示了意想不到的疾病机制。尽管取得了这些成功,但这些已识别的变体仅能解释这些疾病遗传贡献的一小部分,还有更多的变体有待发现。这主要是由于大多数与疾病相关的变体的效应大小较小,以及样本量有限。因此,利用其他信息来更有效地对 GWAS 信号进行优先级排序以提高复制率并更好地了解疾病机制至关重要。在这篇综述中,我们介绍了已发现对 GWAS 后优先级排序有帮助的生物学/基因组特征,并讨论了可用于优先级排序的现有工具。