Major depressive

Major depressive (MD), a prevalent psychiatric condition, was explored through a comprehensive genome-wide association study encompassing 439,605 cases and 1,693,431 controls from European and East Asian backgrounds. This study elucidated the genetic landscape of MD by identifying 217 risk loci, including 49 previously unreported SNVs, and highlighted four SNVs with potential cross-ancestry signals through fine mapping. Our analytical approach integrated various methods to pinpoint 45 credible genes and 29 proteins, alongside 17 classes of drugs that hold therapeutic promise. We developed multiple PGS models, among which the DBSLMM-lmm model excelled in MD risk prediction and exhibited significant gender-based interactions when tested against the UK Biobank. These advancements not only pave the way for fundamental MD research but also enhance the prospects for tailored diagnostics and therapeutics in clinical settings.