Genes and gene networks implicated in aggression related behaviour

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• Aggressive behavior is a significant cause of mortality and morbidity.
• Identifying genetic factors for aggression has been challenging despite moderate heritability.
• Three genetic mouse models exist for studying high and low aggression.

Purpose of the Study:

• To provide a global transcriptomic characterization of the prefrontal cortex in three distinct genetic mouse models of aggression.
• To apply a systems biology approach to uncover neurobiological mechanisms and genetic underpinnings of aggression.
• To identify candidate genes and networks involved in aggression-related behaviors.

Main Methods:

• Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules associated with aggression.
• Ingenuity Pathway Analysis (IPA) for network analysis of identified gene modules.
• RankProd algorithm to evaluate differential gene expression in aggression-related modules.

Main Results:

• WGCNA identified significant gene modules correlated with aggressive behavior across mouse models.
• IPA revealed two key pathways implicated in aggression: NF-kB and MAPKs.
• Differential gene expression analysis identified 14 candidate genes, including Adrbk2, potentially linked to aggression.

Conclusions:

• This study provides novel insights into the neurobiological basis of aggression using a systems biology approach.
• Identified gene networks and pathways offer potential targets for understanding and potentially treating aggression-related disorders.
• The findings highlight specific candidate genes and their roles in aggression, paving the way for future research.