The Complex Trait Genetics group focusses on identifying genetic and neurobiological pathways underlying human complex traits. Complex traits are known to be influenced by multiple genetic and environmental factors as well as interactions between them.
Functional gene groups and complex traits
Research projects within the groups of Verhage, Smit and Cornelisse generate a categorization of genes based on their function in the synapse, as well as a description of the dynamics of genes within a functional group. The Complex Trait Genetics group uses this information to investigate which functional gene groups are important for complex (human) traits, such as ADHD, schizophrenia, obsessive-compulsive disorder, depression or cognitive functioning. We recently showed that genetic variation in the group of heterotrimeric G-proteins is important in explaining individual differences in human cognitive abilities. We currently conduct follow-up analyses to investigate in more detail the genetic mechanism involved. In addition we collaborate with the Erasmus University Rotterdam/Sophia Child Hospital to investigate whether synaptic gene groups are involved in aspects of attentional dysfunctioning.
The interplay of genes and environment in complex traits
We study whether and how environmental measures may impact on genetic influences. This is part of the NESCOG study in which 1000 individuals are tested for cognitive functioning, intelligence, personality traits, various psychiatric behaviors as well as potential environmental moderators. DNA is also being collected. This study is carried out in collaboration with the UvA (Dept. Psychology) and with the GGD Amsterdam.
Genetic influences on brain structure and function
Brain structure and function are thought to mediate the route between genetics and complex traits. To understand how genetic variation influences complex traits, we study the human brain under varying experimental conditions. Our current focus lies on investigating genetically mediated brain functioning important to cognitive ability and we aim to setup similar research projects for other human traits.
Development of statistical methodology for complex genetic associations
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 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 udnerlying structure of multiple traits. These techniques can be applied to available human data or mouse data. disorders, which would benefit from a biologically informed investigation of available GWAS data. Our main focus is therefore to understand differences in brain- and cognitive function, using an integrated molecular genetic approach.
This approach includes biologocially informed genomewide searches in humans for genetic areas that harbour genes for cognition, finemapping of these areas using single nucleotide polymorphisms (SNPs) and confirmation of these SNPs using brain expression analyses in humans and animals.
In addition, confirmation is sought using brain imaging techniques (fMRI) in humans. Several international groups serve as replication platforms for identified genetic variants for cognition. Ultimately we aim to identify gene-cascades involved in molecular mechanisms important for cognition.
Please see also: http://www.cncr.nl/research_teams/complex_trait_genetics/
5 Selected Publications
Vinkhuyzen AA., van der Sluis S., Posthuma D. (2011) Life events moderate variation in cognitive ability (g) in adults. Mol. Psychiatry, 16 (1) : 4-6.
Dupuis J., et al. (2010) Novel genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet., 42 (2) : 105-16.
Ruano D., Abecasis GR., Glaser B., Lips ES., de Jong APH., Evans DM., Davey Smith G., Timpson NJ., Smit AB., Heutink P., Verhage M., Posthuma D. (2010) Functional gene-group analysis reveals a role of synaptic heterotrimeric G-proteins in cognitive ability. Am. J. Hum. Genet., 86 (2) : 113-25.
TAG Consortium. (2010) Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet., 42 (5) : 441-7.
Visscher PM., Posthuma D. (2010) Statistical power to detect genetic loci affecting environmental sensitivity. Behav. Genet.,40 (5) : 728-33.
The Psychiatric GWAS Consortium (2009) A framework for interpreting genomewide association studies of psychiatric disorders. Mol. Psychiatry, 14(1) : 10-7.
A full publication list can be found here.