Genetics, Epigenetics and Bioinformatics

There is a major genetic component in the aetiology of the five disorders investigated. Family and twin studies have documented a high heritability, ranging between 60-80% for schizophrenia, bipolar disorder, autism and ADHD, and around 40% for depression. The underlying genetic architecture is highly complex and polygenic with thousands of common and rare variants influencing disease susceptibility. So far, only a fraction of these variants have been identified.

New technologies enable sequencing of an individual’s complete genome including all 6 billion basepairs within a reasonable cost-and time-frame, and whole genome scannings capturing the majority of the common genetic and epigenetic variation can now be done very fast and cost-effective.

Applying these new technologies we will investigate samples from a large number of patients and healthy controls, including nationwide samples, families, twins, and samples from isolated populations. More than 50,000 cases and 25,000 controls from Denmark will be included in the studies, and a similar number of study subjects from international collaborators is also expected to be included.

The massive data generated is analysed in large high-performance computer clusters using bioinformatics and statistical genetics to unravel the complex correlation between individual’s genetic and epigenetic makeup and the development of mental disease.

The aim is to identify the genes (genetic and epigenetic variants) that confer increased risk as well as those that confer protection against disease development. Also the genes that are influencing other important clinical features such as the long-term outcome, suicide risk, co-morbidity and treatment response are investigated in the studies.

The identification of novel disease associated genes is key to understanding the underlying biology of the disorders, and by integration with the results generated in the other work packages we aim to identify biomarkers and new targets for improved treatment and potentially even prevention of the disorders.

Key collaborative partners in WP2 include Beijing Genomics Institute (BGI) in China and Denmark, Broad Institute in USA, Statens Serum Institut (SSI) in Denmark, deCODE Genetics in Iceland and the Genetic Biobank of the Faroe Islands.