Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Laboratory for Molecular Science for Drug Discovery, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
J Hum Genet. 2021 Jan;66(1):11-23. doi: 10.1038/s10038-020-00845-2. Epub 2020 Sep 18.
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经确定了 >10,000 个与各种表型和疾病相关的遗传变异。虽然大多数是常见的变异，但具有 >0.1%的次要等位基因频率的罕见变异已经通过基因分型和使用特定于疾病的定制 SNP 阵列进行了研究。罕见变异测序分析主要揭示了由于其独特的特征，在人类复杂疾病的遗传学中发挥了独特的作用，与常见变异不同。独特的作用是对基因因果关系的无假设证据，是理解疾病机制的功能分析的精确目标，是药物开发的新有利目标，也是个性化医学中具有高疾病风险的遗传标记。随着全基因组测序不断识别更多的罕见变异，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。
