The disorder is highly heritable, and current treatments often come with challenging side effects.

Over the past 15 years, genome-wide association studies have identified numerous common DNA variants and biomarkers associated with psychiatric disorders, including bipolar disorder.

While common genetic variants contribute a small risk individually, rare loss-of-function variants may offer deeper biological insights into bipolar disorder.

Researchers conducted a variant burden analysis using whole genome sequencing data from Iceland and the UK Biobank, along with validation data from the Bipolar Exomes study.

deCODE genetics, based in Reykjavik, Iceland, specializes in genetic analysis and has uncovered various genetic risk factors for many common diseases.

AKAP11 encodes a protein that anchors regulatory subunits of protein kinase A (PKA), while HECTD2 encodes an E3 ubiquitin ligase that marks proteins for degradation.

Bipolar disorder is characterized by extreme mood swings, including episodes of mania and depression, and carries a significant risk of suicide if left untreated.

Both AKAP11 and HECTD2 interact with GSK3β, a protein inhibited by lithium, the primary mood stabilizer used in bipolar disorder treatment.

The findings suggest that dysfunction in specific cellular pathways related to AKAP11 and HECTD2, along with GSK3β, could be potential targets for developing new treatments for bipolar disorder.

These insights into rare genetic variants and their biological implications may pave the way for innovative therapeutic approaches.