Integrating microarray and sequencing data to identify rare risk and protective genetic variants for schizophrenia.

Fieldrose Charitable Trust PhD Scholarship 2021 - Cardiff University 

Supervisors: Professor James Walters and Dr Elliott Rees

Lay Summary. 

Schizophrenia is typically a severe psychiatric disorder that can have a dramatic impact on the wellbeing of affected individuals and their families. The most common symptoms experienced in people with schizophrenia include hallucinations, delusions, confused thinking, a lack of motivation and impaired cognition. Although the exact biological and environmental causes of schizophrenia are not fully understood, genetics is known to have an important role in its development. However, not everyone with schizophrenia will share the same genetic risk factors, and you can be at elevated genetic risk without developing the disorder; this complexity has made it challenging to identify which genes are involved in schizophrenia.

This project aims to overcome this challenge by investigating how different genetic factors interact with each other in individuals who have been diagnosed with psychosis and schizophrenia. This will enable new approaches to be developed for identifying genes that increase the chance of developing schizophrenia, as well genes that may help explain why some people in high risk groups do not develop schizophrenia. The research also aims to identify genetic factors that contribute to why some people have symptoms that do not improve with current treatments.

The identification of risk genes for schizophrenia will advance our understanding of the underlying biology that, when combined with psychological and social risk factors, can give rise to the condition.  Our hope is that this can lead to the development of better treatments that will have fewer adverse side effects and will help alleviate the distressing symptoms experienced by many people with schizophrenia.

Aims: The project aims to deliver fundamental insights into the pathophysiology of schizophrenia by discovering novel genes associated with the disorder. The co-action between common and rare variants will be evaluated to test the following hypotheses: 

        1) Rare schizophrenia risk variants are enriched among cases with low genetic risk for schizophrenia from common variants 

        2) Rare variants that protect against schizophrenia are enriched among unaffected individuals at high genetic risk for schizophrenia.