Translational genomics and beyond in bipolar disorder

Area of Science:

• Genetics
• Neuroscience
• Psychiatry

Background:

• Genome-wide association studies (GWAS) have identified numerous genomic loci associated with bipolar disorder (BD) risk.
• A significant gap, termed "missing heritability," exists between estimated genetic contributions and GWAS findings, posing challenges for understanding BD's genetic basis.

Purpose of the Study:

• To review the achievements and limitations of current BD GWAS.
• To discuss potential explanations for the "missing heritability" in BD.
• To explore research progress on the biological mechanisms of BD genetic risk.

Main Methods:

• Review of existing literature on GWAS for bipolar disorder.
• Analysis of studies investigating biological mechanisms using brain tissues, reprogrammed cells, and animal models.
• Summarization of findings for key genes implicated in BD (e.g., CACAN1C, ANK3).

Main Results:

• GWAS have advanced understanding of BD genetic risk but have not fully explained heritability.
• Research using diverse biological models is shedding light on gene regulation, brain development, and disease pathophysiology.
• Specific genes like CACAN1C and ANK3 provide insights into potential biological mechanisms of BD.

Conclusions:

• Despite progress, complexities in gene regulation and experimental models necessitate careful consideration.
• Translating GWAS discoveries into understanding BD pathophysiology remains an ongoing challenge.
• Further research is crucial to bridge the gap between genetic findings and the biological underpinnings of bipolar disorder.