Bipolar Disorder
ICD-11: 6A60
Disease Overview
Bipolar disorder is a mood disorder characterized by recurrent episodes of mania or hypomania and depression. Pathophysiology involves dysregulation of monoaminergic and glutamatergic systems, circadian rhythm disruption, and neuroplasticity deficits. Heritability is high (~70–80%); SNP-based h² ~0.25. Key loci include CACNA1C (calcium signaling), ANK3 (ankyrin-G), and genes in dopamine and circadian pathways. Stress, sleep deprivation, and substance use are environmental triggers. Adolescence and early adulthood are peak onset periods.
Onset peaks in late adolescence (15–24). Sleep disruption and substance use in this window amplify risk. Early intervention improves long-term outcomes.
Genetic Architecture Summary
| Gene | Variant | GWAS p | Evidence | Strength |
|---|---|---|---|---|
| CACNA1C | rs1006737 | 1.0e-8 | Voltage-gated calcium channel; neuronal excitability and mood regulation | 0.82 |
| ANK3 | rs10994336 | 5.0e-9 | Ankyrin-G; axon initial segment; neuronal firing | 0.78 |
Heritability
h² SNP: 0.25 — PGC bipolar GWAS (2019)
PRS notes: PRS shows modest discrimination; clinical utility under study.
Exposure Modifier Panel
| Exposure | Direction | Strength | Confidence | Mechanism hypothesis |
|---|---|---|---|---|
| psychosocial-stress | amplify | 0.85 | HIGH | Stress triggers episodes; HPA axis and circadian disruption |
| alcohol | amplify | 0.7 | MEDIUM | — |
Population Equity Notes
GWAS ancestry breakdown: Discovery predominantly European.
Transferability notes: Multi-ancestry efforts ongoing.
Data gaps: Diverse cohorts; G×E in bipolar disorder.
Tissue Context
Visualizations
Risk Shift by Exposure Stratum
Population-level data only — does not predict individual risk
Tissue Relevance
References
- 1.Stahl EA, et al. (2019). Genome-wide association study of bipolar disorder. Nature Genetics. doi:10.1038/s41588-019-0397-8
- 2.Rowland TA, Marwaha S (2018). Environmental risk factors for bipolar disorder. British Journal of Psychiatry. doi:10.1192/bjp.2018.132