Informing precision psychiatry through developing comprehensive genomic models of mental health disorders

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Mental health disorders have a dramatic impact on the wellbeing of affected individuals and their families, and as a result are a leading cause of disability worldwide. Each year in the UK, mental illness affects around 13.5 million people and places a significant burden on the economy through direct (health care) and indirect (lost work and productivity) costs. Although the exact causes of mental health disorders are unknown, a wide range of factors have been found to contribute to their development. For example, many genes are known to significantly influence the development of schizophrenia, and social factors, such as childhood adversity, are also known to have a role. However, no individual cause is by itself necessary or sufficient for the development of mental illness. Moreover, different combinations of risk factors are observed in individuals with the same diagnosis, while the same risk factors are often shared across different disorders. This complexity has made it challenging to study mental health disorders, and a poor understanding of their biological causes has prevented the development of new or more effective treatments. There is also an absence of biologically validated markers for diagnosing patients and identifying individuals who could benefit from more personalised treatments. Another barrier to progress in these areas is that no single type of data can capture all risk factors that influence the development of mental illness. My research aims to address this challenge by integrating different types of biomedical data produced from the same individuals, and developing new methods to simultaneously study the full range of risk factors that contribute to mental ill health. I will initially bring together different types of genetic data, each designed to capture unique forms of genetic variation, from the world's largest schizophrenia samples. This will allow me to provide the most thorough characterisation of genetic variation in schizophrenia to date. I will use these data to discover new risk genes, which will help illuminate the biological causes of schizophrenia. It will also provide molecular targets for the development of new medicines.The symptoms of schizophrenia can vary greatly from person to person, and individuals with the disorder do not always respond to the same treatments. My research aims to identify the genes that influence this variation, which could lead to the development of biomarkers that can be used for providing personalised programmes of treatment. I will also uncover why some genes influence the development of more than one psychiatric disorder, and identify genetic factors that are unique to a specific mental illness. This will be extremely important if genetics is to be used clinically to improve the prediction, diagnosis and prognosis of mental health disorders. My research will also identify genetic factors that protect against the development of psychiatric disorders, as well as explain why some individuals with potent genetic risk factors do not experience mental illness. Understanding this latter phenomenon could point towards new intervention strategies to help prevent people from developing a mental health disorder.The long-term goal of my research is to understand how genes that influence the development of mental health disorders operate alongside additional biological and environmental risk factors. This will provide a more comprehensive understanding of the causes and risks associated with mental illness. I will work closely with clinical colleagues in the NHS and partners in industry to ensure my research is translated into new ways to improve the wellbeing of individuals affected by mental ill health.