Came across this tweet just now:
Polygenic risk scores predict psychosis concordance in twin study, highlighting genetic liability in schizophrenia and bipolar disorder even in small samples.
# Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder
Key Points
Question Is genetic risk for bipolar disorder and schizophrenia (psychosis) associated with twin concordance for these disorders?
Findings In this case-control study including 146 pairs of twins from the Schizophrenia and Bipolar Twin Study in Sweden and 21 356 pairs of twins from the Swedish Twin Registry, polygenic risk scores for psychosis (ie, schizophrenia or bipolar disorder) were associated with case status and twin concordance, although concordance did not depend on zygosity.
Meaning Using the natural experiment of twins, results suggest that genetic liability carries predictive power for psychosis, even in a small sample.
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.