Association of COL25A1 with comorbid antisocial personality disorder and substance dependence

Biol Psychiatry. 2012 Apr 15;71(8):733-40. doi: 10.1016/j.biopsych.2011.12.011. Epub 2012 Jan 31.


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 and European Americans (smallest p values were .0002 and .0004, respectively). There was also evidence of association with the same SNP in independent samples of African American and European American cases and control subjects (p = .035 and .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 = .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 amyloid β 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antisocial Personality Disorder / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Diagnosis, Dual (Psychiatry)
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Non-Fibrillar Collagens / genetics*
  • Polymorphism, Single Nucleotide
  • Substance-Related Disorders / genetics*


  • COL25A1 protein, human
  • Non-Fibrillar Collagens