This study analyzed exome sequencing data from 454,787 UK Biobank participants, identifying over 12 million coding variants and finding 564 genes associated with nearly 500 health-related traits. Most of these associations were independent of common variant signals found in genome-wide association studies, highlighting the potential of exome sequencing to pinpoint rare variants that influence disease risk and other traits.

The authors declare that some are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals.

This study represents a significant contribution to the field of human genetics due to its large sample size and comprehensive analysis of exome sequencing data. The identification of rare variant associations with a wide range of traits provides valuable insights into gene function and potential therapeutic targets. While limitations regarding genetic diversity, phenotyping methods, and lack of family data exist, these are acknowledged by the authors and do not detract from the overall quality and impact of the research.