Background
Antisocial Personality Disorder (ASPD) is a psychiatric disorder characterized by a long-term pattern of manipulating, exploiting or violating the rights of others.
Methods
Subjects ascertained for genetic studies of substance dependence (SD) and diagnosed with ASPD and comorbid SD were included in a two-stage genetic association study. In the discovery stage, 627 single nucleotide polymorphisms (SNPs) located in 179 candidate genes for addiction were analyzed in a case-control cohort and family-based cohort. The significant findings were replicated in an independent case-control cohort.
Results
One SNP, rs13134663, in the collagen XXV alpha 1 gene (COL25A1), was significantly associated with ASPD in both African-Americans (AAs) and European Americans (EAs) (smallest P values were 0.0002 and 0.0004, respectively). There was also evidence of association with the same SNP in independent samples of AA and EA cases and controls (P = 0.035 and 0.033, respectively). Analysis of the combined set of case-control subjects yielded an allelic P value of 9×10−6 with odds ratio (95% confidence interval) of 1.3 (1.16, 1.47) (smallest P = 1×10−7; Bonferroni threshold P = 0.00012).
Conclusions
The COL25A1 gene, located at chromosome 4q25, encodes the collagen-like Alzheimer amyloid plaque component precursor, a type II transmembrane protein specifically expressed in neurons; it co-localizes with Aβ in senile plaques in Alzheimer disease brains. This SNP maps to the transcription factor binding site and is conserved in 17 vertebrates, including mice and rats. Our findings suggest that COL25A1 may be associated with ASPD, especially in the context of SD.