The UK10K project identifies rare variants in health and disease. It sequenced whole genomes and exomes of nearly 10,000 individuals to uncover rare and low-frequency genetic variants associated with health traits. The project characterized over 24 million novel variants, developed an accurate imputation reference panel, and identified novel alleles linked to triglycerides, adiponectin, and LDL cholesterol. It also explored population structure, functional annotation, and the benefits of sequencing for association studies. The project provided extensive resources, including genetic and phenotypic data and web-based tools for exploring association results. The UK10K project aimed to study the contribution of rare and low-frequency variation in the UK population to a range of biomedically relevant traits and diseases. It included two main arms: the UK10K-cohorts arm, which sequenced 3,781 individuals from two European ancestry cohorts, and the UK10K-exomes arm, which sequenced approximately 6,000 individuals from three collections. The UK10K-cohorts arm identified 24 million novel SNVs, INDELs, and large deletions, while the UK10K-exomes arm identified causal mutations in rare diseases, severe obesity, and neurodevelopmental disorders. The project found that rare variants are underrepresented in existing genetic studies and require direct sequencing for accurate identification. It also demonstrated that the UK10K haplotype reference panel significantly improves imputation accuracy and coverage for low-frequency and rare variants compared to existing panels. The project identified novel associations with lipid and adiponectin traits, and showed that rare variants have limited impact on population trait variation. It also highlighted the importance of incorporating functional genome information in association tests for non-coding regions. The UK10K project provided valuable insights into the role of rare and low-frequency variation in human complex traits and will inform future association studies. It also emphasized the need for larger sample sizes and better understanding of allelic architecture to improve study power. The project's findings support the importance of rare variants in health and disease and highlight the value of large-scale sequencing data for complex traits. The project's resources, including genetic and phenotypic data and web-based tools, are available for further research.The UK10K project identifies rare variants in health and disease. It sequenced whole genomes and exomes of nearly 10,000 individuals to uncover rare and low-frequency genetic variants associated with health traits. The project characterized over 24 million novel variants, developed an accurate imputation reference panel, and identified novel alleles linked to triglycerides, adiponectin, and LDL cholesterol. It also explored population structure, functional annotation, and the benefits of sequencing for association studies. The project provided extensive resources, including genetic and phenotypic data and web-based tools for exploring association results. The UK10K project aimed to study the contribution of rare and low-frequency variation in the UK population to a range of biomedically relevant traits and diseases. It included two main arms: the UK10K-cohorts arm, which sequenced 3,781 individuals from two European ancestry cohorts, and the UK10K-exomes arm, which sequenced approximately 6,000 individuals from three collections. The UK10K-cohorts arm identified 24 million novel SNVs, INDELs, and large deletions, while the UK10K-exomes arm identified causal mutations in rare diseases, severe obesity, and neurodevelopmental disorders. The project found that rare variants are underrepresented in existing genetic studies and require direct sequencing for accurate identification. It also demonstrated that the UK10K haplotype reference panel significantly improves imputation accuracy and coverage for low-frequency and rare variants compared to existing panels. The project identified novel associations with lipid and adiponectin traits, and showed that rare variants have limited impact on population trait variation. It also highlighted the importance of incorporating functional genome information in association tests for non-coding regions. The UK10K project provided valuable insights into the role of rare and low-frequency variation in human complex traits and will inform future association studies. It also emphasized the need for larger sample sizes and better understanding of allelic architecture to improve study power. The project's findings support the importance of rare variants in health and disease and highlight the value of large-scale sequencing data for complex traits. The project's resources, including genetic and phenotypic data and web-based tools, are available for further research.