Genetic Epidemiology of Brain Traits and Neuropsychiatric Disorders

Understanding the genetic mechanisms underlying the way the brain functions in general and dysfunctions in disease is very complex. Reasons behind this include the clinical/functional heterogeneity of brain related diseases/traits and the fact that they show a complex etiology. This means that combinations of many common genetic variants with small effect sizes interacting with each other and with the environment are involved.

Our goal is to find genes involved in the variation of brain traits as well as for genes involved in the risk of complex neuropsychiatric diseases. In order to do this we combine a series of state-of-the-art approaches. First, we have a very strong network of collaborators. We make part of the core analysis group of the world's biggest brain imaging genetics consortium, the ENIGMA consortium (enigma.loni.ucla.edu). Through this collaboration, we recently identified common genetic variation significantly associated with the variance of hippocampus and intracranial volumes.

We are currently working on indentifying the genes associated with multiple subcortical volumes in a sample of over 25,000 individuals all around the world. Second, and since the study of single genetic variants is not powerful enough in disease association studies, we apply alternative gene-finding methodology to profit from combined genetic effects. From this approach we have been able to detect an association of the SORL1 gene (a candidate gene for Alzheimer's disease) associated with hippocampal volume in healthy young adults.

We also detected the association between the Dopamine/Noradrenalin and Serotonin genetic pathways with symptom counts and behavioral traits associated with Attention Deficits Hyperactivity Disorder.