Program leaders:            Danielle Posthuma, Hanne Meijers
Taskforce team:              Matthijs Verhage
Program members

Rationale and common goals

This program explores the genetic, epigenetic and environmental causes of individual differences in brain function and dysfunction related to cognitive, mental and physical health. In the past decade major advances in technology (e.g. microarrays, next generation sequencing, brain imaging, induced pluripotent stem cells) in a number of fields have been made, which led to unprecedented leaps forward in our knowledge and understanding of the genetic architecture of brain disorders. Progress in genotyping technology have been paralleled by a reduction of costs and an increase of datasets and sample sizes available for research. Large-scale genetic studies provided novel insights and keys for functional and pharmaceutical follow-up.

In the coming years sample sizes for genetic association discovery analyses are expected to increase and yield an increasing amount of reliable genetic discoveries. Interpreting these ‘hits’ in their polygenic context and using them to guide functional experiments is a major focus of our research program. A key focus is on understanding genetic mechanisms underlying single psychiatric traits as well as co-morbidities between multiple traits. Our current research projects revolve around schizophrenia (SZ) , obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), substance use and substance dependence, mental retardation, autism, RETT syndrome, depression and dementia.

The main goals of the Complex Trait Genetics research program are:

  • To develop and apply statistical tools for the analyses of genetic data;
  • To develop and apply bioinformatics tools integrating biological information with outcomes from genetic studies;
  • To develop and apply a pipeline for integrating knowledge from Mendelian forms of a disorder with polygenic forms of a disorder;
  • To develop and apply pipelines for genetically informed prioritization for follow-up functional research.

Assets

  • The Genetics Cluster Computer (http://www.geneticcluster.org) (Dept. Complex Trait Genetics, VUmc);
  • The genomics facility of AMC and VUmc delivers services for large scale genome analyses (e.g. whole exome sequencing in collaboration with the foundation HMF whole genome sequencing), RNA sequencing and epigenic analyses;
  • The desk of Clinical Genetics provides a platform where clinicians and scientists meet on a monthly basis to discuss patient cases and possibilities for follow-up research;
  • The stem cell lab (http://www.ipscenter.nl) provides induced pluripotent stem (IPS) cell lines for patients and controls, which can be differentiated into glial or neuronal cell types;
  • Cohorts of patients with Mendelian inherited diseases due to high-risk alleles will serve as a source to dissect complex traits. Cohorts of patients with mental retardation with unknown cause after whole exome sequencing;
  • A cohort of approximately three thousand patients annually with familial causes of brain related disorders;

Making the difference? 

The Complex Trait Genetics program:

  • Facilitates gene-discovery using innovative statistical and bioinformatics tools;
  • Guides functional follow-up by prioritizing genes, and genetic pathways;
  • Provides high throughput genotyping facilities and large scale computing power for genetic discovery studies.