A number of studies have demonstrated a familial relationship between depression and antisocial personality disorder (ASPD). We examined the possibility that major depression (MD) and ASPD share genetic influences.
Participants were 1,054 twins from the Vietnam Era Twin Registry (mean age 41.5 years (+2.34)). They were administered the Diagnostic Interview Schedule III-R from which number of lifetime symptoms of MD, dysthymia, and ASPD were derived. We examined the relationship of polygenic risk scores (PRS) for depression to symptoms of MD, dysthymia, and ASPD. PRS was based on weights derived from a GWAS of MD. PRSs were computed at a range of P-value thresholds. Results are reported for the most significant threshold of p < 0.2, which included 53,972 SNPs. We controlled for non-independence of twins using mixed models; age and race/ethnicity were used as covariates. All analyses adjusted for the first 3 principal components from SNP data to account for any cryptic population substructure.
The MD PRS was significantly associated (p<.05) with the lifetime number of symptoms of MD, dysthymia, and ASPD. We then examined the relationship of the PRS to individual ASPD symptoms. The most significant association was with the symptom of irritable and aggressive behavior (p<.01). There was also a trend (p<.10) for associations with starting fights, using a weapon in fights, and failure to conform to social norms. We investigated whether childhood SES moderates the relationship between genetic risk for depression and ASPD. We found a significant interaction between the PRS and childhood SES (p=.02). The relationship between depression PRS and ASPD was stronger among those raised in a lower SES environment.
Although the magnitudes of the associations that we observed were relatively modest, very often PRSs do not explain a great deal of the variance, even in the phenotype from which they were derived.
