title: Genes and gene networks implicated in aggression related behaviour.
abstract: Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour.
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK, karim.malki@kcl.ac.uk.
authors.forename: Karim
authors.initials: K
authors.lastname: Malki
authors.forename: Oliver
authors.initials: O
authors.lastname: Pain
authors.forename: Ebba
authors.initials: E
authors.lastname: Du Rietz
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tosto
authors.forename: Jose
authors.initials: J
authors.lastname: Paya-Cano
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Sandnabba
authors.forename: Sietse
authors.initials: S
authors.lastname: de Boer
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.forename: Frans
authors.initials: F
authors.lastname: Sluyter
mesh_terms: D000374:Aggression / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism*