Polygenic risk score
Bipolar Disorder
ICD-11 6A60 · Mood disorders
The bipolar disorder polygenic risk score summarizes common-variant liability from the largest bipolar GWAS ever assembled — nearly 3 million participants. The PRS is well-powered for statistical inference but predicts modest variance in liability at the individual level.
The 2025 PGC bipolar GWAS includes ~158,000 cases and 2.8 million controls — the largest single-trait psychiatric GWAS published — identifying 298 independent loci.
At a glance
Bipolar disorder is highly heritable and shares substantial genetic overlap with schizophrenia and depression. Your score reflects the latest PGC bipolar GWAS published in Nature in 2024.
Bipolar disorder is a recurrent mood disorder involving episodes of mania or hypomania alternating with depression. Heritability is around 60-85%. The 2024 PGC bipolar GWAS analyzed the largest sample to date across type I, type II, and schizoaffective subtypes, refining the genetic architecture and the overlap with related conditions.
What the GWAS actually found
The 2025 PGC bipolar meta-analysis (O'Connell et al., Nature) combined 158,036 bipolar cases and roughly 2.8 million controls to identify 298 independent genome-wide significant loci. The effective sample size makes it one of the best-powered psychiatric GWAS to date.
Twin-study heritability for bipolar disorder sits at approximately 0.60–0.85, with substantial overlap in common-variant architecture with schizophrenia (rg ≈ 0.70) and major depressive disorder. The shared architecture reflects the cross-disorder nature of psychiatric genetic risk.
Full citation: Latest PGC Bipolar Disorder GWAS (2024). Nature. PMID: 39843750. Largest published bipolar GWAS to date..
How to read your percentile
Below 25th
Lower common-variant liability than most of the reference cohort. Does not rule out bipolar disorder — mood-disorder onset is strongly shaped by environmental triggers.
25th–75th
Typical range. Your score is near the population average; bipolar disorder remains uncommon (~1–2% lifetime prevalence).
Above 75th
Elevated common-variant liability. Interpret as one input alongside family history and mood-course observations. Early recognition of hypomanic episodes remains the clinical priority.
What this does not tell you
A bipolar PRS does not distinguish Bipolar I (with manic episodes) from Bipolar II (with hypomanic episodes) cleanly, and it cannot identify cyclothymia or subthreshold bipolar-spectrum presentations. Clinical subtyping remains the domain of psychiatric interview and mood-charting.
The score cannot predict timing of first episode, severity, response to lithium, or conversion from unipolar depression to bipolar disorder. Cross-ancestry accuracy is reduced in non-European populations, and rare highly penetrant variants — while rarer in bipolar than in schizophrenia — are not captured by a common-variant PRS.
Related traits
Bipolar Disorder shares common-variant architecture with several other psychiatric conditions. Genetic correlations (rg) reflect how often the same variants move risk for both traits in the same direction.
Frequently asked questions
Does this score distinguish Bipolar I from Bipolar II?
Not cleanly. The 2025 PGC GWAS pooled Bipolar I, Bipolar II, and schizoaffective bipolar type. Type-specific PRS are emerging in research contexts but are not what this report scores. Clinical subtyping remains the domain of psychiatric evaluation.
Can this score predict whether I will respond to lithium?
No. Lithium response prediction is an active research area but is not captured by a standard bipolar PRS. Response-specific PRS and pharmacogenomic markers are distinct from disease-liability PRS.
I have depression — does a high bipolar PRS mean I'll develop mania?
A high bipolar PRS modestly elevates the probability of a depressive episode being later reclassified as bipolar, but the predictive power for an individual is low. Clinical monitoring — not a PRS — determines conversion from unipolar to bipolar-spectrum.
How much does the bipolar PRS overlap with schizophrenia?
Substantial overlap — the cross-disorder genetic correlation between bipolar and schizophrenia is approximately 0.70. Many genome-wide significant loci are shared. This reflects real biological overlap in the psychosis-mood spectrum, not a methodological artifact.
Sources
- O'Connell et al. 2025, Nature 639:xxx. doi.org/10.1038/s41586-024-08468-9
- PGC Bipolar Disorder Working Group. pgc.unc.edu/for-researchers/working-groups/bipolar-disorder-workgroup/
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