Alison Barton’s paper on whole-exome imputation and subsequent association and fine-mapping analyses in UK Biobank (Barton et al. 2021 Nat Genet) is now published — congratulations, Alison! Imputation is a statistical approach that leverages genetic data from a reference panel to enable analysis of genetic variants that are not directly measured in a cohort, thereby expanding the utility of existing data sets without incurring additional cost. In the past, this approach has primarily been applied to variants that are commonly observed in a population, but in this work, we showed that with a sufficiently large, well-matched reference panel, imputation is an effective strategy for analyses of very rare coding variants (which traditionally have been viewed as only accessible via direct sequencing). Here, we imputed rare coding variants from the first N=50K UK Biobank exomes into the remainder of the cohort (total N=500K), enabling identification of 1,189 significant, likely-causal genotype-phenotype associations involving 675 distinct rare protein-altering variants, many with large effect sizes. These analyses also demonstrated the importance of accounting for linkage disequilibrium even when analyzing rare coding variants and when performing gene burden analyses. [GenomeWeb news story]