Translational genomics and beyond in bipolar disorder

Mol Psychiatry. 2021 Jan;26(1):186-202. doi: 10.1038/s41380-020-0782-9. Epub 2020 May 18.


Genome-wide association studies (GWAS) have revealed multiple genomic loci conferring risk of bipolar disorder (BD), providing hints for its underlying pathobiology. However, there are still remaining questions to answer. For example, discordance exists between BD heritability estimated with earlier epidemiological evidence and that calculated based on common GWAS variations. Where is the "missing heritability"? How can we explain the biology of the disease based on genetic findings? In this review, we summarize the accomplishments and limitations of current BD GWAS, and discuss potential reasons for the "missing heritability." In addition, progresses of research for the biological mechanisms underlying BD genetic risk using brain tissues, reprogrammed cells, and model animals are reviewed. While our knowledge of BD genetic basis is significantly promoted by these efforts, the complexities of gene regulation in the genome, the spatial-temporal heterogeneity during brain development, and the limitations of different experimental models should always be considered. Notably, several genes have been widely studied given their relatively well-characterized involvement in BD (e.g., CACAN1C and ANK3), and findings of these genes are summarized to both outline possible biological mechanisms of BD and describe examples of translating GWAS discoveries into the pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bipolar Disorder / genetics*
  • Bipolar Disorder / physiopathology
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Genomics*
  • Humans