Impact of Genetic Risk Factors on People With Schizophrenia

Principal investigator: Dr James Walters

Location: UK

Research award: Mental Health Data Science

Funding Period: 2018-2020

On average, people with schizophrenia die 20 years earlier than the general population.

To tackle this, we need to build a deeper understanding of the condition, including how it affects physical health.

In recent years, we have gained important insights into genetic risk factors for schizophrenia. But we don’t yet know how these factors affect specific symptoms or the physical health of someone with schizophrenia. This information could enable us to create tailored interventions informed by genetics.

Dr James Walters and his team at Cardiff University are finding out – combining genetic, health and social data to build the evidence for better, targeted treatments for schizophrenia.

The project

This project, led by James Walters at Cardiff University, set out to investigate the impact of genetic risk factors specifically copy number variants (CNVs) on physical health in people with schizophrenia.

By linking large-scale genetic data with health informatics records, the research aimed to clarify whether the increased rates of physical illness observed in schizophrenia are attributable to underlying genetic liability.

The study involved both clinically ascertained samples and population data, with a particular focus on the effects of CNVs that are known to increase risk for schizophrenia and other neurodevelopmental disorders.

The process

James and his team linked genetic data from individuals with schizophrenia to anonymised NHS health records in Wales. This incorporated genetic data from 6,000 people with schizophrenia – but didn’t include clinical information such as the background of patients, the kinds of symptoms experienced or any indication of how severe their condition is.

The project also analysed data from the UK Biobank to assess the broader impact of schizophrenia-associated CNVs on physical health in the general population.

This meant that for the first time, the study linked genetic data to pre-existing clinical NHS data so we gain a far greater understanding of the real-life impact that genetics can have on schizophrenia.

James and the team also wanted tol determine what physical health problems, like cardiovascular disease and obesity, are associated with genetic factors in people living with schizophrenia.

The outcome

The research confirmed that individuals with schizophrenia experience markedly poorer physical health compared to the general population, with increased rates of epilepsy, intellectual disability, type 2 diabetes, congenital disorders, ischaemic heart disease, and smoking.

In the general population, CNVs that increase risk for schizophrenia were also associated with a higher risk of various physical illnesses, especially cardiometabolic conditions.

However, the study found no strong evidence that genetic liability for schizophrenia (including CNVs) explains the increased rates of physical illness seen in people with the disorder.

The project established a valuable resource of linked genetic and health data, which will support future research.

The impact

This research has important implications for clinical practice, policy, and future studies. By demonstrating that genetic risk factors for schizophrenia do not substantially account for the physical health disparities seen in affected individuals, the project shifts the focus towards lifestyle, medication, and other modifiable factors in managing physical health in schizophrenia.

The creation of linked datasets and the establishment of new clinical genetics services, such as psychiatric genetics clinics offering counselling and testing, provide direct benefits to patients and families, empowering them with information and support.

The project also lays the groundwork for further research, including expanded data linkage and collaboration, and has already led to additional funding and partnerships. More broadly, this approach exemplifies how integrating genetic and health informatics data can drive advances in understanding, prevention, and care for people with severe mental illness.

For future reports, it is essential to highlight not only the scientific and clinical impacts but also the ways in which research fosters patient involvement, informs service development, and contributes to public health and policy improvements.

Dr James Walters

Dr James Walters is a researcher in the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University. His research focuses on genetics and schizophrenia.