Polygenic risk score
Cross-Disorder Psychiatric (PGC-CDG)
Cross-Disorder · Shared psychiatric axis
The Cross-Disorder polygenic score summarizes the shared common-variant axis underlying multiple psychiatric conditions — what the PGC Cross-Disorder Group calls the 'general psychopathology factor'. It captures risk that is not specific to any one diagnosis.
The Cross-Disorder score captures shared common-variant liability across eight psychiatric disorders — schizophrenia, bipolar, MDD, ADHD, autism, OCD, anorexia, Tourette — pointing to a common 'general psychopathology' axis of genetic risk.
At a glance
The PGC Cross-Disorder GWAS pools cases across multiple psychiatric diagnoses to find shared genetic risk. Your score reflects loading on this shared psychiatric risk axis.
The Cross-Disorder Group GWAS analyzes shared common-variant risk across schizophrenia, bipolar disorder, depression, ADHD, autism, anxiety, and related conditions. The output identifies genomic loci that influence general psychiatric liability rather than any single diagnosis. The 2025 version is the latest update to this analysis.
What the GWAS actually found
The PGC Cross-Disorder Group analysis (Lee et al. 2019, Cell) pooled GWAS data across eight psychiatric disorders to identify loci contributing to shared rather than disorder-specific liability. The analysis revealed 109 pleiotropic loci and genetic correlations including SCZ–BIP (0.70), OCD–Anorexia (0.50), ADHD–MDD (0.44), and ADHD–ASD (0.36).
Subsequent Grotzinger 2022 analyses using genomic structural equation modeling identified three underlying factors: a compulsive factor (OCD, Tourette, anorexia), a mood-psychosis factor (SCZ, BIP, MDD), and a neurodevelopmental factor (ADHD, autism). The cross-disorder PRS captures loading on this shared axis — complementary to, not replacing, per-trait scoring.
Full citation: Latest PGC Cross-Disorder Group GWAS (2025). Pooled analysis across psychiatric phenotypes. See https://pgc.unc.edu/ for the canonical publication.
How to read your percentile
Below 25th
Lower common-variant loading on the shared psychiatric axis than most of the reference cohort. Per-trait PRS remain independently informative.
25th–75th
Typical range — near the population average. Per-trait scores are where the specific signal lives.
Above 75th
Elevated shared loading. Interpret alongside per-trait PRS — someone high on both the cross-disorder axis and a specific trait has a stronger combined signal than either alone.
What this does not tell you
The cross-disorder score is not a 'general psychiatric risk' number in the clinical sense — it captures the shared genetic axis, but individual disorder risk still depends on disorder-specific architecture. A high cross-disorder score does not mean elevated risk for every psychiatric condition; a low score does not mean immunity.
Interpretation is most useful as a complement to per-trait PRS: someone high on the cross-disorder axis AND high on a specific trait PRS has a stronger combined signal than either alone. Clinical application of cross-disorder scoring is still emerging.
Related traits
Cross-Disorder Psychiatric (PGC-CDG) 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
What does the cross-disorder score mean for me?
It captures shared common-variant liability across multiple psychiatric conditions. A high score suggests elevated loading on the general psychiatric axis, but does not imply equal risk for every disorder — individual PRS for each trait carry the disorder-specific signal.
Is this the same as a 'mental illness' PRS?
Not exactly. The cross-disorder axis captures pleiotropic common variants — genetic influences that cut across diagnostic lines. It's closer to a shared-architecture score than a generic 'mental illness risk' score, and does not substitute for per-trait PRS.
Which psychiatric traits load most on the cross-disorder factor?
Schizophrenia and bipolar disorder are the strongest contributors, followed by MDD and ADHD. OCD and anorexia load on a related compulsive-spectrum factor. Autism and Tourette sit on the neurodevelopmental factor.
Should I worry about elevated cross-disorder loading?
No. The score is a population-level probabilistic signal across multiple conditions — not a diagnosis, not an imminent risk indicator. Its practical value is as a complement to per-trait interpretation, not a standalone health metric.
Sources
- Lee et al. 2019, Cell 179:1469–1482. doi.org/10.1016/j.cell.2019.11.020
- Grotzinger et al. 2022 — Genomic structural equation modeling. doi.org/10.1038/s41588-022-01057-4
- PGC Cross-Disorder Working Group. pgc.unc.edu/for-researchers/working-groups/cross-disorder-workgroup/
Note: This trait references a recent or pre-publication GWAS. Specific cohort numbers, loci counts, and variance-explained estimates on this page will be refined when the final peer-reviewed source is published. The product uses summary statistics from the source cited above.
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