| Title: | Genetic risk of psychopathology predicts environmental risk |
| Journal: | Schizophrenia |
| Published: | 6 Oct 2026 |
| DOI: | https://doi.org/10.1038/s41537-026-00805-3 |
| URL: | https://www.nature.com/articles/s41537-026-00805-3_reference.pdf |
Publication 21628
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Abstract
Environmental risk factors for psychosis and psychopathology are often treated as non-genetic, although many are partly heritable or correlated with genetically influenced traits. We tested nine polygenic scores against 49 environmental-risk factors in 307,493 UK Biobank participants without recorded schizophrenia, bipolar disorder, or major depressive disorder diagnoses or antipsychotic medication use. Polygenic scores were generated using PRS-CS and tested in 441 standardised linear models with HC1 robust standard errors. Across all models, 212 associations survived within-score false-discovery-rate correction. ADHD, educational attainment, major depression, schizophrenia and bipolar disorder polygenic scores showed the broadest profiles, but associations differed across five environmental-risk categories. In a secondary analysis excluding victimisation and behavioural measures, seven perception/subjectivity factors showed stronger pooled associations than 25 objective/non-perception factors for schizophrenia, major depression, ADHD, bipolar disorder and neuroticism polygenic scores. Four conceptually tighter matched comparisons produced a similar but non-uniform pattern. Effects were small and do not establish causality. Measured environmental risk is partly correlated with inherited liability through behavioural, social, socioeconomic, cognitive, and perception-related pathways.</p>
5 Authors
- Adam Socrates
- Jessie R. Baldwin
- Robin M. Murray
- Paul F. O'Reilly
- Jean-Baptiste Pingault
1 Application
| Application ID | Title |
|---|---|
| 18177 | Multi-trait GWAS analyses in the UK Biobank |
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