The UK10K project aims to identify rare and low-frequency variants contributing to human traits and diseases. The project sequenced whole genomes (7× read depth) or exomes (80× read depth) of nearly 10,000 individuals from population-based and disease collections. Over 24 million novel sequence variants were characterized, and a highly accurate imputation reference panel was generated. The study identified novel alleles associated with triglycerides, adiponectin, and low-density lipoprotein cholesterol levels. The project also assessed population structure and functional annotation of rare and low-frequency variants, estimated the benefits of sequencing for association studies, and provided web-based tools for exploring association results. The UK10K haplotype reference panel significantly improved imputation accuracy and coverage for low-frequency and rare variants compared to existing panels. The study found limited evidence of confounding by population stratification at the traits investigated, suggesting a weakening of historical patterns of population structure in the UK population. Overall, the UK10K project has generated valuable genomic tools and insights into the role of rare and low-frequency variants in complex traits and diseases.The UK10K project aims to identify rare and low-frequency variants contributing to human traits and diseases. The project sequenced whole genomes (7× read depth) or exomes (80× read depth) of nearly 10,000 individuals from population-based and disease collections. Over 24 million novel sequence variants were characterized, and a highly accurate imputation reference panel was generated. The study identified novel alleles associated with triglycerides, adiponectin, and low-density lipoprotein cholesterol levels. The project also assessed population structure and functional annotation of rare and low-frequency variants, estimated the benefits of sequencing for association studies, and provided web-based tools for exploring association results. The UK10K haplotype reference panel significantly improved imputation accuracy and coverage for low-frequency and rare variants compared to existing panels. The study found limited evidence of confounding by population stratification at the traits investigated, suggesting a weakening of historical patterns of population structure in the UK population. Overall, the UK10K project has generated valuable genomic tools and insights into the role of rare and low-frequency variants in complex traits and diseases.