Institute for Genomic Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, USA.
Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Nat Rev Genet. 2019 Dec;20(12):747-759. doi: 10.1038/s41576-019-0177-4. Epub 2019 Oct 11.
The first phase of genome-wide association studies (GWAS) assessed the role of common variation in human disease. Advances optimizing and economizing high-throughput sequencing have enabled a second phase of association studies that assess the contribution of rare variation to complex disease in all protein-coding genes. Unlike the early microarray-based studies, sequencing-based studies catalogue the full range of genetic variation, including the evolutionarily youngest forms. Although the experience with common variants helped establish relevant standards for genome-wide studies, the analysis of rare variation introduces several challenges that require novel analysis approaches.
全基因组关联研究（GWAS）的第一阶段评估了常见变异在人类疾病中的作用。优化和节约高通量测序的进展使评估所有蛋白质编码基因中稀有变异对复杂疾病的贡献的第二阶段关联研究成为可能。与早期基于微阵列的研究不同，基于测序的研究对遗传变异进行了全面分类，包括进化史上最年轻的形式。虽然常见变体的经验有助于为全基因组研究建立相关标准，但稀有变体的分析提出了一些需要新的分析方法的挑战。
