689. What genetics research has told us about the mechanisms of mood disorders

Abstract

Abstract Background Prior to the advent of large scale genome wide association studies, substantial investments generally failed to reveal major insights into the genetic architecture of mood disorders. Reasons for this include a lack of methodological and data harmonisation, small study sizes and a lack of replication, collaboration and meta-analysis. Aims & Objectives Using data from 20 years of the international Psychiatric Genomics Consortium, I will review progress in this field and present our current knowledge, and opportunities for us to deepen our understanding in future. Method Genome wide association study of common genetic variants have advanced greatly in the last 20 years. Here, I will present published and unpublished insights into the genetics and genomics of mood disorders from GWAS studies, presenting data on individual discoveries, mechanistic insights and how these discoveries have and could be leveraged in basic and clinical research and practice. Results The PGC has revealed more than 700 genetic variants for depression and bipolar disorder with many common genes implicated across these conditions and schizophrenia. Many individual mechanisms have been proposed and investigated and polygenic risk scores can now stratify risk in individuals and groups in ways that allow other types of approach (e.g. brain imaging). Discussion & Conclusions We need to continue to head the lessons learned by the PGC and expand their approaches more broadly across other areas of research. Collaboration and data sharing has been a major driver of the accelerating progress in this field.