Lithium response in bipolar disorder: Genetics, genomics, and beyond.

• Clinical response to lithium treatment in bipolar disorder is heterogeneous. • Genetics may explain such a heterogeneity. • Genomic approaches have already identified suggestive regions in our DNA associated with lithium response. • Recent advances in cellular models, high throughput analysis, and statistical methodologies may catalyze advances in this field. Lithium is an effective mood stabilizer in bipolar disorder (BD). There is, however, high variability in treatment response to lithium and only 20–30% of individuals with BD are excellent responders. This subgroup has been shown to have specific phenotypic characteristics, and family studies have implicated genetics as an important factor. However, candidate gene studies did not find evidence for major effect genes. Genome-wide association studies (GWAS) have emphasized that lithium response is a polygenic trait. GWAS based on larger sample sizes and non-European ancestries are likely to shed light on the genomic architecture of this trait. Furthermore, induced pluripotent stem cells, transcriptomics, epigenetics, the integration of multiple omics data, and their combination with advanced machine learning techniques hold promise for the understanding of the complex biological underpinnings of lithium treatment response. [ABSTRACT FROM AUTHOR]