Genetic association studies of aggression-related genes

Abstract

Suicidal behavior is a major health problem worldwide. The risk of suicide-related behavior is supposed to be determined by a complex interplay of sociocultural factors, traumatic life experiences, psychiatric history, personality traits, and genetic vulnerability. This view is supported by adoption and family studies indicating that suicidal acts have a genetic contribution that is independent of the heritability of Axis I and II psychopathology. Neurobiological studies have shown that serotonergic dysfunction is implicated in suicidal behaviors. Additionally aggression-related traits are mediated by the serotonergic system. Since both, aggression−related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. Thus, we also investigated the relationship between serotonergic genes and anger, as a subtype of aggression-related behavior.

For that reasons we have initiated a large scale case control genetic association study which comprises of 250 suicide attempters and 1900 healthy volunteers and investigated the role of a comprehensive set of serotonergic candidate genes in this behavior. Additionally we conducted a large-scale gene expression analysis using cDNA-microarrays to identify new candidate-genes for suicide. We found several genes to be differentially expressed in the orbitofrontal cortex of suicide completers. Cross-validation experiments using quantitative RT-PCR validated 9 genes so far. These genes were genotyped as well to look for associations with suicide-, anger- and aggression-related behavior and also these results will be presented.