Franklin C, et al. - Genetic complexity and pathogenetic mechanisms related to bipolar disorder (BPD), a highly heritable psychiatric disorder, are still not clear. Via performing this work, researchers sought to characterize BPD risk-gene candidates (identified by Nurnberger et al., JAMA Psychiatry 71:657, 2014, and Stahl et al., Nat. Genet. 51:793, 2019) concerning their evolutionary conservation, associated phenotypes, and extent of gene-gene interactions. Across species, BPD risk genes are highly conserved and are enriched for essential genes and genes linked with lethality and altered life span. These genes are noted to be significantly more interactive with each other relative to random genes. Syntenic blocks of risk genes were identified, which yielded potential insights into molecular pathways and co-morbidities linked with BPD including coronary disease, obesity, and reduced life expectancy. Seemingly, BPD risk genes were exceptional regarding their degree of conservation, interconnectedness, and pleiotropic effects that extend beyond a role in brain function. For future drug discovery, key hub genes or pleiotropic regulatory components are suggested as attractive targets.