The aim of the project is to improve understanding of the molecular basis of bipolar disorder (BD). To achieve this, research groups at the Universities of Basel (Switzerland) and Bonn (Germany) will apply innovative strategies and complementary expertise. In a functional approach, induced pluripotent stem cell (iPSC)-derived neural cells from selected BD patients and controls will be used to identify disease-associated transcriptomic and cellular signatures that are attributable to combinations of known common risk variants within neurodevelopmental pathways (Gene Ontology (GO)-term informed polygenic risk score analysis (PRS)). In parallel, rare novel risk variants with higher penetrance will be identified in multiply affected families with BD that were selected based on the potential for stronger genetic effects on neurodevelopmental processes. In a subsequent funding phase, we plan to introduce these variants into the iPSCs of BD patients and controls with differing PRS backgrounds.