Using polygenic scores to assess liability to antisocial behavior.

Area of Science:

• Behavioral Genetics
• Forensic Psychiatry
• Population Genetics

Background:

• Genome-wide association studies (GWAS) have identified genetic variants associated with antisocial behavior (ASB) in European populations.
• Polygenic scores (PGS) aggregate effects of multiple genetic variants to predict complex traits.
• Replication of ASB genetic findings in non-European populations is crucial for generalizability.

Purpose of the Study:

• To replicate findings on liability to severe criminal behavior (homicide) in a Russian cohort using PGS.
• To identify the best predictive model for ASB liability incorporating PGS and social factors.
• To assess the relative contributions of genetic and social factors to ASB risk.

Main Methods:

• Genotyping of ten single nucleotide polymorphisms (SNPs) previously associated with ASB in GWAS.
• Real-time PCR used for genotyping in 227 homicide offenders and 254 controls from Russia.
• Multiple regression models analyzed weighted and unweighted PGS alongside social predictors.

Main Results:

• PGS explained a small proportion of variance (1.1-1.5%) in ASB liability.
• Social factors, including traumatic brain injury, chronic disease, and smoking, significantly predicted ASB.
• The best model combining genetic and social factors explained 16.2-21.2% of the variance.
• Family history of mental illness amplified the impact of these factors.

Conclusions:

• Social factors have a greater impact than the tested SNPs on predicting ASB liability in this Russian cohort.
• Comorbid substance abuse, traumatic brain injury, and family history of mental illness are linked to higher ASB probability.
• These social factors may reflect an underlying 'risky' genetic profile, warranting further investigation.