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.



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.

Research Student: Sophie Chick


Hello, I’m Sophie, and I will be starting my PhD at the Cardiff MRC Centre for Neuropsychiatric Genetics and Genomics in July 2021, under the supervision of Dr Elliott Rees and Professor James Walters.

I completed my Bachelor’s degree in Genetics at the University of Sheffield, where I developed an interest in psychiatric genetics. I found the complex genetics of psychiatric disorders fascinating, and was drawn to research in this area by the fact that the underlying molecular mechanisms are not yet known. During my Master’s degree in Human Molecular Genetics at Imperial College, I carried out a six-month research project at the University of Cambridge Autism Research Centre. In this project I investigated heterogeneity in autism, by analysing genetic correlations between autistic traits to test whether they are influenced by different sets of common genetic factors.

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Analysing common variation as part of this project fostered my interest in using a combined approach to integrate both common and rare variation. I am extremely excited to have the opportunity to develop methods for joint analysis of common and rare variants in schizophrenia, with the aim of improving understanding of its underlying causes and providing new targets for development of treatments. I look forward to working with Dr Rees and Professor Walters, and would like to express my immense gratitude to Mental Health Research UK for funding this project.