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Common genetic biological pathways for mental illnesses

Posted on 20/01/2015
Psychiatric disorders share genetic risk factors

Genetic analysis of 60,000 people has found that psychiatric disorders such as schizophrenia, bipolar disorder and major depression share biological pathways, according to new research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) published this week in Nature Neuroscience.

Thousands of genetic differences across the human genome act together to increase the risk for psychiatric conditions but, until now, it has not been clear how these genetic changes affect different biological processes that then go on to alter brain function. Genetic data was analysed from tens of thousands of participants including individuals with schizophrenia, bipolar disorder, major depression, autism spectrum disorders and attention deficit hyperactivity disorder, as well as healthy individuals with the aim of identifying the biological and biochemical pathways that were risk factors for these disorders.

“When we grouped the genetic data together, we found that genes relating to histone methylation - molecular changes that alter DNA expression – and to immune function are risk factors associated with the development of these disorders,” said Dr Gerome Breen of the MRC Centre for Social Genetic and Developmental Psychiatry, IoPPN, and a lead author of the study. He went on to emphasise that biological pathways are important as they are much broader drug targets than single genes or proteins.

The study was conducted by the Pathways Subgroup of the Psychiatric Genomics Consortium, which was founded in 2007 and involves work from hundreds of investigators from dozens of institutions across the globe. As well as Dr Breen, the study was led by Professor Peter Holmans at Cardiff University, in collaboration with researchers at UCLA and the Broad Institute of Harvard and MIT. 

Professor Holmans noted: “The use of genome-wide genetic data allows us to identify disease-relevant pathways without making prior biological assumptions. This is important as it enables us to discover novel mechanisms of risk that might not otherwise be studied.”

The histone pathways investigated weren’t just prevalent across common psychiatric disorders, they have also been studied previously in relation to cancer and infectious diseases and the new evidence is an important step in determining ways to develop new therapeutic approaches towards these critical pathways. 

Dr Breen concluded: “This is a particularly exciting development in the study of psychiatric disease as it is a first step in identifying shared biological mechanisms that act across disorders. This will help in developing treatments that target these mechanisms, and are thus effective for a range of psychiatric illness, irrespective of exact diagnosis.”

Paper reference: Authored by the Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium ‘Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways’ published in Nature Neuroscience DOI: 10.1038/nn.3922

For further information contact Tom Bragg, Press Officer at IoPPN, King’s College London, on +44(0)2078485377 or email ioppn-pr@kcl.ac.uk

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