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INTPART-International Partnerships for Excellent Education and Research

Integrating analytical tools with brain imaging and genetics in mental illness research and education

Alternative title: Integrere analyseverktøy med hjerneavbildning og genetikk i mental helse forskning og utdannelse

Awarded: NOK 3.8 mill.

Many distinct psychiatric diseases share a common genetic structure, according to new research by scientists University of Oslo and the Psychiatric Genomics Consortium, an international team of investigators. Psychiatric disorders affect more than 25 percent of the population in a given year. In the largest-ever study of its kind, published in the journal Cell, researchers identified more than 100 genetic variants that affect the risk for more than one mental health condition. A gene is made up of segments of DNA; an alteration in the DNA sequence produces a gene variant, which can increase or decrease the risk for disease. Many individual gene variants that affect the risk for specific psychiatric disorders have been identified. However, genes are often pleiotropic, meaning they produce multiple effects in the body. Identifying gene variants that influence the risk for more than one psychiatric disorder is an important step toward improving the diagnosis and treatment of these conditions, says the study?s Norwegian Principle investigator and part of the writing group, Ole A. Andreassen, MD, PhD, director of NORMENT, University of Oslo and Oslo University Hospital. ?Understanding how specific genetic variations may contribute to a broad spectrum of illnesses can tell us something about the degree to which these disorders may have a shared biology,? says Andreassen. To identify these multi-purpose gene variants, the researchers used a technique called genome-wide association to analyze genetic data from 494,162 healthy control subjects and 232,964 people diagnosed with at least one of eight common psychiatric disorders. The analysis identified 109 gene variants that affect the risk for more than one psychiatric disorder. Certain disorders shared many variants, allowing the researchers to divide the conditions into three groups of genetically-related conditions: disorders characterized by compulsive behaviors (anorexia nervosa, obsessive-compulsive disorder and, to a lesser extent, Tourette syndrome); mood and psychotic disorders (bipolar disorder, major depression and schizophrenia); and early-onset neurodevelopmental disorders (autism spectrum disorder, ADHD and Tourette syndrome). The researchers also found evidence that genes associated with multiple disorders show increased expression beginning in the second trimester of pregnancy and appear to play an important role in brain development. Knowing which gene variants increase the odds for developing multiple psychiatric disorders provides new clues about the biological pathways that contribute to mental illness, says Andreassen. ?And learning how disorders are related at a biological level may inform how we classify and diagnose mental health conditions,? he says . Moreover, the study identified several gene variants that had especially widespread influence on the risk for a number of psychiatric disorders, which could prove to be an important finding for the prevention and care of psychiatric disorders. ?To the extent that these genes may have broad effects,? says Andreassen, ?they could be potential targets for developing new treatments that might benefit multiple conditions.?

The project has led to a series of research projects, grants, and training of PhD students and post docs. In addition, it has led to several strategic advantages for UiO, related to content relevant for the future related to research training as well as research programs. The project has led to an increased focus on research exchange and training opportunities in the US for younger researchers. In addition, UCSD researchers have been informed about the advantages of Norwegian research infrastructure including biobanks and registries, and health care. Further, the project has led to high level of scientific output in the groups involved in the team. NORMENT has increased the expertise both in imaging and genetics, including large scale analytical approaches. The younger researchers have also been connected with informal networks and partners. Further, the US partners have been included in several projects, and grant applications, both nationally and internationally.

The mental disorders (including schizophrenia, bipolar disorder) are ranked among the leading causes of the burden of diseases worldwide. Thus, identifying their underlying pathophysiology is imperative and can lead to major health benefits. The current project focuses on improving the education of our future scientists within Centre of Excellence NORMENT (University of Oslo, UiO) and its clinical, brain imaging and genetics teams, based on frontline collaborative research projects with University of California, San Diego (UCSD), USA. The program will develop a strong synergy between the clinical/biomedicine expertise of NORMENT; and the engineering/analytical expertise at Centre Transl Imaging Person Medicine (CTIPM). We will integrate education and research about brain and genetic mechanisms involved in mental illness, and new statistical / bioinformatics tools, to form a strong framework for excellent research. The project builds on a strong collaboration between the UiO (NORMENT) and UCSD (CTIPM). The education and training proposed in this grant naturally build on the technologies developed in the CTIPM at UCSD, with applications that are likely to have transformative impact in a number of areas of fundamental importance to basic and clinical science, particularly mental health. We will focus on genetics, brain imaging and outcome, three areas of importance for NORMENT, where novel computational and biostatistical methods will be of importance. The project builds on existing collaboration between UiO and UCSD in natural sciences, and will extend this into Life Sciences, focusing on mental illness. Research in Life Science is currently exploding, mainly as a result of technological developments. To fully exploit this, the project will develop new methods that make it possible to extract relevant information from large data sources (big data) and be able to interpret the impact in a clinical setting. The project provides a framework for long-term collaboration.

Funding scheme:

INTPART-International Partnerships for Excellent Education and Research