Research
Functional Gene Networks for Brain Disorders
Brain disorders are amongst the most pressing health problems in today’s western society. Despite the fact that most brain disorders are highly heritable, only few disease genes have been identified so far. The lack of insight into genetic variation implicated in brain disease is a major obstacle for the design of effective therapeutic strategies.
To alleviate the problems of small genetic effect sizes and multiple testing accompanying single-SNP GWA analyses, we have developed an alternative way to model multiple small genetic effects by evaluating the combined, additive effects of variations in multiple, functionally related genes. We investigate whether these groups of functionally related genes are involved in several brain disorders.
Researchers involved: Lips, Min, Posthuma
Funded by: ZonMW-TOP (CI Posthuma, with Niels Cornelisse (PI), Tom Heskens and Matthijs Verhage), EU SynSys, Sophia Stichting, VU-NCA
Imaging and Genetics of Cognitive Phenotypes
Understanding how genetic variation affects cognitive traits, such as intelligence or ADHD, is one of the greatest scientific challenges of the 21st century. In this project we combine brain imaging and genetics to understand how genetic pathways influence cognitive behavior by altering brain structure or function.
Researchers involved: Rizzi, Chavarria-Siles, Posthuma
Funded by: NWO-open competition (Posthuma, Fernandez), NWO-VIDI (Posthuma), VU-CNCR, NWO-NIHC (Posthuma)
The Genetics of Mild Intellectual Disability
Intellectual disability affects around 2-3% of the world population. It is broadly defined as ‘significant limitations both in cognitive ability and in adaptive behaviour as expressed in conceptual, social and practical adaptive skills’. Within the total group of the intellectually disabled, the majority (60%-85%) is classified as mild. Current research, however, mainly focuses on severe and/or syndromic intellectual disability. In addition, current research methodology aims to identify monogenetic causes (mainly X-linked genes) or genomic deletions/duplications.
In this project we focus on identifying genetic and environmental causes of mild, non-syndromic intellectual disability.
Researchers involved: Beunders, Posthuma
Funded by: VUMC, VU-NCA
The Genetics of ADHD
Attentionâ€deficit/hyperactivity disorder (ADHD) is a neurobehavioral developmental
disorder, affecting 3â€7% of children. It is characterized by a persistent pattern of
impulsiveness and inattention, with or without hyperactivity. Twin studies
indicate that ADHD is highly heritable. However, genomeâ€wideâ€association studies have
failed to reliably identify genetic variants that explain even a small part of the genetic
risk. Most likely, the combination of many genetic variants explains the vulnerability to
ADHD.
In this project we investigate which genetic pathways and functional gene networks underly ADHD symptoms and a clinical diagnosis of ADHD.
Researchers involved: Polderman, Posthuma
Funded by: VU-NCA, VU, NWO-NIHC (Posthuma)
Development of novel statistical techniques for genetic analysis
The recent rapid advances in genotyping technology need to be parallelled by advances in statistical methodology. The Complex Trait Genetics group identifies current gaps in statistical methodology and develops novel models and software/scripts that aid in identifying genetic and neurobiological pathways underlying complex traits. We focus on analysing genome-wide association data using datamining techniques, developing methods to detect the genetic control of environmental or phenotypic variability and using factor analytic methods to determine the underlying structure of multiple traits. These techniques can be applied to available human data or mouse data. 
Researchers involved: van der Sluis, Aarts, Min, Posthuma
Funded by: NWO-Veni (van der Sluis), NWO-VIDI (Posthuma), NWO-Complexity (Cornelisse, Posthuma, Heskens, Verhage)
The Genetic Cluster Computer
The past five years have seen an explosive growth in the scale at which human genetic research takes place in terms of sample size, number of traits and availability of genetic marker information. This has led to a parallel increase in the demand on computing power. Access to high computing power is therefore crucial to our understanding of human complex traits.
The Genetic Cluster Computer (GCC) was set-up to meet this need for high computing power in genetic research. In the spirit of open source software and sharing knowledge and resources, we have made access to the GCC available to national and international researchers within the field of genetics. We also teach beginning users how to work within a UNIX environment and how to use the cluster efficiently. The GCC is hosted by SARA Computing and Networking Services .
Researchers involved: Posthuma
Funded by: NWO-Investments (Posthuma), Dutch Brain Foundation (Ophoff), Psychiatric Genetics Consortium (Sullivan), VU
Population based cohort - NESCOG study
Intelligence is a highly heritable trait for which only a handful of genes have been implicated together explaining much less than the total heritability. The Netherlands Study of Cognition, Genes and Environment (NESCOG) was set up to investigate the underlying genetic mechanisms of intelligence as well as to investigate potential interactions of genes with environmental factors relevant to intelligence.
The NESCOG study is a large-scaled, population based study in which currently (2010) more than 2000 adults and children have participated. From all individuals measures of cognitive behavior have been collected as well as questionnaires on environmental factors. From most adult individuals DNA has also been collected. Part of the NESCOG data collection has been carried out in collaboration with the science center NEMO .
Researchers involved: Rizzi, Chavarria-Siles, Polderman, van der Sluis, Posthuma
Funded by: NWO-VIDI (Posthuma)
Research Methods
We use ‘wet’ genetic techniques (DNA isolation, (GWAS)-genotyping, sequencing), ‘in silico’ genetic techniques, statistical genetic techniques and neuroimaging techniques.