Genetic Research into Bipolar Disorder: The Need for a Research Framework that Integrates Sophisticated Molecular Biology and Clinically Informed Phenotype Characterization

Research into the genetic basis of bipolar disorder (BD) has reached a turning point. Genome-wide association studies (GWAS), encompassing several thousand samples, have produced replicated evidence for some novel susceptibility genes; however, the genetic variants implicated so far account for only a fraction of disease liability, a phenomenon not limited to psychiatric phenotypes but characteristic of all complex genetic traits studied to date. It appears that pure genomic approaches, such as GWAS alone, will not suffice to unravel the genetic basis of a complex illness like BD. Genomic approaches will need to be complemented by a variety of strategies, including phenomics, epigenomics, pharmacogenomics, and neurobiology, as well as the study of environmental factors. This review highlights the most promising findings from recent GWAS and candidate gene studies in BD. It furthermore sketches out a potential research framework integrating various lines of research into the molecular biological basis of BD.