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.

中文翻译：

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复杂特征的稀有变异折叠分析：指南和应用。

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关联研究的第二阶段成为可能，该研究评估罕见变异对所有蛋白质编码基因中复杂疾病的贡献。与早期的基于微阵列的研究不同，基于测序的研究对所有的遗传变异进行了分类，包括进化上最年轻的形式。尽管常见变异的经验有助于建立全基因组研究的相关标准，但罕见变异的分析引入了一些需要新分析方法的挑战。