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Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder
Jie Song1,2,3, Joëlle A Pasman2,3, Viktoria Johansson3,4
1Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
JAMA Psychiatry
|August 28, 2024
Summary
Individuals with a higher polygenic risk score (PRS) for psychosis had a greater likelihood of having an affected co-twin. This genetic liability for psychosis demonstrated predictive power, even in smaller sample sizes.
Area of Science:
- Psychiatric Genetics
- Twin Studies
- Molecular Psychiatry
Background:
- Schizophrenia and bipolar disorder share high heritability and genetic factors.
- Twin and molecular genetic methods can identify shared genetic liabilities for these disorders.
- Understanding genetic overlap is crucial for predicting psychosis risk.
Purpose of the Study:
- To determine if twin concordance for psychosis correlates with polygenic risk score (PRS) for psychosis and zygosity.
- To compare PRS between psychosis cases and controls.
- To estimate the twin heritability of psychosis.
Main Methods:
- A case-control study utilizing twin data from the Schizophrenia and Bipolar Twin Study (STAR) and the Swedish Twin Registry.
- Polygenic risk scores (PRS) for psychosis were generated from a genome-wide association study (GWAS) combining schizophrenia and bipolar disorder.
- Structural equation modeling was used to estimate heritability.
Main Results:
- Psychosis PRS were significantly higher in cases compared to controls.
- Higher PRS for psychosis was associated with increased twin concordance for psychosis.
- Twin heritability for psychosis was estimated at 0.73, consistent across different cohorts.
Conclusions:
- Genetic liability for psychosis, as measured by PRS, predicts the likelihood of an affected co-twin.
- PRS holds predictive value for psychosis, independent of zygosity.
- Findings from twin and molecular designs align, reinforcing the role of genetic factors in psychosis.
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