Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder
Bibliographic record
Abstract
Importance: Schizophrenia and bipolar disorder are highly heritable psychiatric disorders with strong genetic and phenotypic overlap. Twin and molecular methods can be leveraged to predict the shared genetic liability to these disorders. Objective: To investigate whether twin concordance for psychosis depends on the level of polygenic risk score (PRS) for psychosis and zygosity and compare PRS from cases and controls from several large samples and estimate the twin heritability of psychosis. Design, Setting, and Participants: In this case-control study, psychosis PRS were generated from a genome-wide association study (GWAS) combining schizophrenia and bipolar disorder into a single psychosis phenotype and compared between cases and controls from the Schizophrenia and Bipolar Twin Study in Sweden (STAR) project. Further tests were conducted to ascertain if twin concordance for psychosis depended on the mean PRS for psychosis. Structural equation modeling was used to estimate heritability. This study constituted an analysis of existing clinical and population datasets with genotype and/or twin data. Included were twins from the STAR cohort and from the Swedish Twin Registry. Data were collected during the 2006 to 2013 period and analyzed from March 2023 to June 2024. Exposures: PRS for psychosis based on the most recent GWAS of combined schizophrenia/bipolar disorder. Main Outcomes and Measures: Psychosis case status was assessed by clinical interviews and/or Swedish National Register data. Results: The final cohort comprised 87 pairs of twins with 1 or both affected and 59 unaffected pairs from the STAR project (for a total of 292 twins) as well as 443 pairs with 1 or both affected and 20 913 unaffected pairs from the Swedish Twin Registry. Among the 292 twins (mean [SD] birth year, 1960 [10.8] years; 158 female [54.1%]; 134 male [45.9%]), 134 were monozygotic twins, and 158 were dyzygotic twins. PRS for psychosis was higher in cases than in controls and associated with twin concordance for psychosis (1-SD increase in PRS, odds ratio [OR], 2.12; 95% CI, 1.23-3.87 on case status in monozygotic twins and OR, 2.74; 95% CI, 1.56-5.30 in dizygotic twins). The association between PRS for psychosis and concordance was not modified by zygosity. The twin heritability was estimated at 0.73 (95% CI, 0.30-1.00), which overlapped with the estimate in the full Swedish Twin Registry (0.69; 95% CI, 0.43-0.85). Conclusions and Relevance: In this case-control study, using the natural experiment of twins, results suggest that twins with greater inherited liability for psychosis were more likely to have an affected co-twin. Results from twin and molecular designs largely aligned. Even as illness vulnerability is not solely genetic, PRS carried predictive power for psychosis even in a modest sample size.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.015 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".