Polygenic risks and cardiovascular treatment effects in severe mental illness
Kai Yao1, Alexandra Burton2, Samira Heinkel3
1Molecular Psychiatry Laboratory, Division of Psychiatry, Faculty of Brain Sciences, University College London.
Psychiatric Genetics
|October 29, 2025
Summary
Polygenic risk scores (PRS) show promise for predicting cardiovascular risks in severe mental illness (SMI). However, their predictive power for certain measures like LDL cholesterol may change after cardiovascular interventions in SMI patients.
Area of Science:
- Genetics and Cardiovascular Health
- Psychiatric Disorders and Public Health
Background:
- Individuals with severe mental illness (SMI) face elevated cardiovascular disease (CVD) risks, contributing to reduced life expectancy.
- Polygenic risk scores (PRS) offer a potential tool for stratifying CVD risk.
- Understanding the interplay between genetic predisposition and lifestyle interventions is crucial for managing CVD in SMI populations.
Purpose of the Study:
- To assess the predictive capability of cardiovascular PRS for various cardiovascular risk factors in patients with SMI.
- To investigate the impact of cardiovascular interventions on the predictive accuracy of PRS over time.
- To explore potential interactions between genetic risk and treatment outcomes.
Main Methods:
- Utilized data from the PRIMROSE programme, which included longitudinal cardiovascular interventions.
- Calculated seven cardiovascular PRS and two psychiatric PRS (bipolar, schizophrenia).
- Applied multiple linear regression models to analyze associations between PRS and cardiovascular measures (lipids, blood pressure, BMI) at baseline and 12-month follow-up.
Main Results:
- Cardiovascular PRS generally predicted corresponding measures at baseline, with exceptions like LDL cholesterol.
- Following interventions, improvements were observed in total cholesterol and systolic blood pressure, with PRS predictive effects diminishing.
- A notable finding was a negative association between bipolar PRS and LDL cholesterol post-treatment, suggesting a potential protective effect in higher-risk individuals.
Conclusions:
- Genetic risk assessment timing is critical, as PRS predictive utility can be influenced by cardiovascular interventions in SMI patients.
- The study highlights the dynamic relationship between genetic predisposition and treatment response in managing cardiovascular health in SMI.
- Further research is needed to elucidate subtype-specific genetic interactions with interventions for personalized risk management.
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