Understanding genetic contributions to mental health

Most psychiatric disorders have a genetic underpinning – people with a family history of depression are twice as likely to develop depression themselves, and those with relatives with schizophrenia are up to eight times as likely to develop schizophrenia.

Large scale genetic studies have identified specific genetic variants that contribute to the risk of developing a disease. Polygenic traits are caused by thousands of genes, each contributing a small amount of risk and we now have tools that combine these genetic effects into a single polygenic score. The score estimates an individual’s genetic risk of developing a disorder. Polygenic scores, first applied in schizophrenia research, are now used to study a range of diseases and disorders.

Polygenic Scores

Researchers at the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre investigate how polygenic scores can predict risk and also help us understand the role of genetics in psychiatry. For example, some of the genetic contribution to depression is relevant to other psychiatric disorders, and people who have two or more episodes of depression often have a stronger genetic predisposition than people who have only a single episode.

Our team has contributed extensively to the methods and analysis aspects of polygenic scores, releasing publicly available statistical software tools, e.g., PRSice is fast, easy-to-use software for calculating and analysing polygenic scores. It is widely used, and the software has been cited 700 times in publications worldwide.

Clinical Application

We also develop software for the clinical application of polygenic scores, and our webtool (figure below) allows accurate interpretation of an individual’s polygenic score. The BRC has also contributed to a free online polygenic score calculator, ‘Impute.me’, which provides an educational resource to estimate genetic risk for many disorders. Our software tools are all openly available online and used by research groups worldwide, across many branches of medicine.

 Diagram: Interactive webtool which allows accurate interpretation of an individual’s polygenic score 

Currently, polygenic scores enable teams to use genetics in research studies. Further evidence is needed to support clinical implementation and the first clinical trials are underway. As knowledge of the genetic contribution to mental health increases, genetics will facilitate precision medicine approaches by indicating better treatments or identifying individuals at increased risk of developing a disorder. The BRC team will continue to develop novel statistical models and software to drive forward the clinical use of genetic data.

Read more about polygenic scores in our blog, Genetics helps us estimate the risk of disease - but how much does it really tell us? by Cathryn Lewis, Professor of Genetic Epidemiology & Statistics, King's College London and Oliver Pain, Postdoctoral Research Associate, King's College London.



Developing Resources for Research | Personalising Treatment to Patients