Identifying the genetic risk factors for psychiatric disorders - Norwegian part of the Psychiatric Genomics Consortium

Psychiatric and substance use disorders are caused by both genetic and environmental factors. We know that the role of genetics, or heritability, in these disorders is significant, although it varies from disorder to disorder. Heritability refers to how much of the trait can be explained by genetic factors (as opposed to environmental factors). For example, autism spectrum disorders, bipolar disorder and schizophrenia are highly heritable (i.e. genetics play a large role), while the heritability of disorders such as major depressive disorder is significantly lower (i.e. genetics play a minor role). Genetic factors do not cause psychiatric disorders in themselves, but can increase a person's risk of developing the disorder. Psychiatric and substance use disorders are polygenic, meaning that many genes act together to increase a person's risk for a disorder. This is similar to characteristics such as height. There is not one gene for depression, anxiety, depression or any other disorder, but many hundreds and perhaps several thousand variants that contribute to risk. By uniting the global research community, the Psychiatric Genomics Consortium (PGC) advances our understanding of the genetics of psychiatric and substance abuse disorders. It has been known for some time that genetic influences play an important role in why some people are more likely to be affected by psychiatric or substance abuse disorders than others. However, we knew very little about the specific genes that make someone more vulnerable. By collecting genetic data from hundreds of thousands of individuals around the world, the PGC works to find the genetic variants that change the risk of disease. Identifying the genetic basis of these disorders helps us to understand the underlying biology and to develop better ways to prevent and treat disorders. This project has supported the Norwegian part of the PGC, which is one of the largest, most innovative and productive studies in the history of psychiatry. The central idea of ??the PGC is to use a global collaborative network to advance genetic discovery to identify biologically, clinically and therapeutically meaningful insights. Through the Norwegian sub-project of the PGC, we have helped to unite the field and attract outstanding researchers to the PGC, which now consists of over 800 investigators from 150 institutions in more than 40 countries. PGC has so far led to over 300 articles, many in high-profile journals (Nature, Cell, Science, Nature Genetics, Nature Neuroscience, Molecular Psychiatry, Biological Psychiatry, JAMA Psychiatry. The full results of all PGC articles are freely available, and the findings of the project have contributed to a number of follow-up studies and advanced the careers of many younger researchers. The Norwegian sub-study has contributed to results in PGC by collecting data, contributing to analyses, interpretation of data as well as writing reports and publications.

Studien har bidradd til ny kunnskap om genetiske sårbarhetsfaktorer ved psykiske lidelser. Dette gir ny innsikt i sykdomsmekanismer, og kan bidra til utvikling av nye medikamenter. Prosjektet har gitt en serie med internasjonale publikasjoner i ledende internasjonale tidsskrift. Videre vil resultatene om overlappende genetiske faktorer bidra til bedre forståelse av klassifisering av psykiske lidelser (nosologi). Prosjektet har også bidratt til at norske forskere har fått en stor kompetanseheving innen stordata og beregningsvitenskap, samt tilgang til internasjonalt nettverk.

Psychiatric disorders are leading causes of morbidity globally, and are costly disorders. Identifying the underlying pathophysiology is imperative and can lead to major health benefits, through better treatment and prevention strategies. Genome-wide association studies (GWAS) have identified many trait-associated gene loci and have been very successful in psychiatry. However, only a small fraction of genetic variance has been identified. This missing heritability has been attributed to inadequate sample sizes (low power), and lack of proper statistical methods for analysis of the polygenic architecture. Together with the large international Psychiatric Genomics Consortium (PGC), we will apply our new statistical methods (Bayesian enrichment tools) and large samples from PGC to uncover more of the missing heritability of psychiatric disorders. The current project includes genotype data from more than 50 000 Norwegian samples, and a total of nearly 1 million samples globally. This will provide large opportunities for novel discoveries in psychiatric etiology. We will investigate 9 psychiatric disorders, from child and adolescence to old age psychiatry. The present grant will fund the Norwegian parts of the PGC activities, including data analysis, development of novel analytical tools, genotyping and data collection. The current project is based on several Norwegian groups involved in psychiatric genetics, and will fund a post doc who will become an European node for the PGC analytical team, closely integrated with the activities of the NIH funded main PGC grant. The project will facilitate the development of excellent research environments, with a long-term potential for future studies based on Norwegian advantages, the human biobank and registry datasets. The project answers important research questions as outlined in the Mental Health and Addiction Research Program.