Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arrays. Rare variants sequencing analysis mainly revealed have played unique roles in the genetics of complex diseases in humans due to their distinctive features, in contrast to common variants. Unique roles are hypothesis-free evidence for gene causality, a precise target of functional analysis for understanding disease mechanisms, a new favorable target for drug development, and a genetic marker with high disease risk for personalized medicine. As whole-genome sequencing continues to identify more rare variants, the roles associated with rare variants will also increase. However, a better estimation of the functional impact of rare variants across whole genome is needed to enhance their contribution to improvements in human health.

全基因组关联研究已识别出超过 10,000 个与各种表型和疾病相关的遗传变异。尽管大多数是常见变异，但已通过插补和使用疾病特异性定制 SNP 阵列对次要等位基因频率 >0.1% 的罕见变异进行了研究。罕见变异测序分析主要揭示了与常见变异相比，由于其独特的特征，它们在人类复杂疾病的遗传学中发挥着独特的作用。独特的作用是基因因果关系的无假设证据、了解疾病机制的功能分析的精确目标、药物开发的新有利目标以及个性化医疗的具有高疾病风险的遗传标记。随着全基因组测序不断发现更多罕见变异，与罕见变异相关的作用也将增加。然而，需要更好地估计整个基因组中罕见变异的功能影响，以增强它们对改善人类健康的贡献。