Shared genetics between addiction, aggression, and related behavioural traits

Substance use disorders (SUD) and aggressive behaviour often co-occur within individuals, along with transdiagnostic behavioural traits such as risk-taking behaviour, impulsivity, irritability, neuroticism, or anxiety. This study investigates shared genetic risk factors across these phenotypes using public genome-wide association study (GWAS) data: five GWAS on SUD, two on aggressive behaviour, and seven on related behavioural traits. We calculated genetic correlations and identified trait-specific associated SNPs shared between these phenotypes using Polarmorphism. Also, we determined how the genetic bases of aggressive behaviour or related traits contribute to SUD using polygenic risk scores (PRS).High genetic correlations (rg > 0.61) were found among the five SUD datasets, which were all also positively correlated with drug experimentation (rg:0.57-0.82) and risk taking (0.35-0.46). Interestingly, datasets on antisocial behaviour and disruptive behaviour disorders (DBD) showed high genetic correlations with SUD (rg: 0.50-0.55). The SUD dataset also correlated positively with impulsivity, irritability, neuroticism and risk taking (rg: 0.13-0.4). DBD positively correlated with irritability, neuroticism, and risk taking (rg: 0.25-0.36). Shared SNPs with direct effects were identified for SUD and risk taking (2602 SNPs), SUD and irritability (4856 SNPs), SUD and neuroticism (6913 SNPs), as well as DBD and risk taking (297 SNPs). PRS revealed significant associations between risk taking and SUD, indicating that genetic risk variants for risk taking, as well as DBD, contribute to increased SUD severity (dependence on more substances of abuse).Overall, this study elucidates common genetic variants contributing to addiction, aggression, and related behavioural traits providing insights into their shared genetic liability.