Major depression (MD) is a leading cause of worldwide disability and affects approximately 15% of the global population during their lifetime. The peak age of onset is in early adulthood, and the disorder is typically recurrent or chronic in nature, often with persisting disability despite pharmacological and psychological therapies. Twin and family-based studies provide evidence of a significant genetic contribution to its etiology, with a heritability of approximately 37%.1 Since 2013, genome-wide association studies (GWASs) have provided major insights into the polygenic nature of MD, its genetic risk factors, and underlying mechanisms.2–9 The largest study conducted to date reported 243 independent MD risk loci from a meta-analysis of the Million Veteran Program (MVP), 23andMe, UK Biobank, FinnGen, and iPSYCH, including 371K cases.10
