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.
Key Words
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Article info
Publication history
Published online: February 02, 2012
Accepted:
December 13,
2011
Received in revised form:
December 12,
2011
Received:
September 15,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
