Nature. 2025 Aug 6. doi: 10.1038/s41586-025-09272-9.
Whole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort. This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health.
全基因组测序提供了对人类基因组无偏差的完整视图，并且能够发现遗传变异，而不受其他基因分型技术的技术限制。在此，我们基于之前的基因分型工作，报告了对490,640名英国生物银行参与者的全基因组测序结果。这一进展加深了我们对遗传学与疾病生物学之间关联的理解，并进一步提升了这个开放资源在人类生物学和健康研究中的价值。将这个数据集与丰富的表型数据相结合，我们研究了族内和跨族裔的基因组关联，并获得了新的遗传学和临床见解。尽管大多数与疾病特征的关联主要在欧洲血统个体中观察到，但在非洲和亚洲血统个体中也发现了强烈或新的信号。随着准确对结构变异以及编码和非翻译区（UTR）序列中的外显子变异进行基因分型的能力得到提高，相对于全外显子测序分析，我们强化并揭示了新的见解。这个数据集代表了英国生物银行研究群体可获取的大量全基因组测序数据，将推动我们对人类基因组的理解取得进展，促进发现疗效更高、安全性更好的诊断方法和治疗手段，并实现有可能改善全球健康状况的精准医学策略。
