Whole-exome sequencing in the UK Biobank has revealed a rare genetic architecture for depression. This finding is part of a broader trend of research into the genetic underpinnings of various diseases and traits, with studies also examining the genetic architecture of conditions such as postpartum psychosis, amyotrophic lateral sclerosis, and heart failure. The use of whole-exome and whole-genome sequencing is helping to shed light on the role of rare and common genetic variations in human disease.