Association of COL25A1 with Comorbid Antisocial Personality Disorder and Substance Dependence

Li, Dawei; Zhao, Hongyu; Kranzler, Henry R.; Oslin, David; Anton, Raymond F.; Farrer, Lindsay A.; Gelernter, Joel

doi:10.1016/j.biopsych.2011.12.011

« Previous Next »Biological Psychiatry
Volume 71, Issue 8 , Pages 733-740, 15 April 2012

Association of COL25A1 with Comorbid Antisocial Personality Disorder and Substance Dependence

Dawei Li
- Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut
Hongyu Zhao
- Department of Epidemiology and Public Health, School of Medicine, Yale University, New Haven, Connecticut
- Department of Genetics, School of Medicine, Yale University, New Haven, Connecticut
Henry R. Kranzler
- Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- Veterans Integrated Service Network 4, Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania
David Oslin
- Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- Veterans Integrated Service Network 4, Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania
Raymond F. Anton
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina
Lindsay A. Farrer
- Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Genetics and Genomics, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts
Joel Gelernter
- Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut
- Department of Genetics, School of Medicine, Yale University, New Haven, Connecticut
- Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
- Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut
- Address correspondence to Joel Gelernter, M.D., Yale University School of Medicine, Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, 950 Campbell Avenue, 116A2, West Haven, CT 06516

Received 15 September 2011; received in revised form 12 December 2011; accepted 13 December 2011. published online 02 February 2012.

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: Addiction , amyloid plaque , antisocial personality disorder (ASPD) , association , collagen XXV alpha 1 (COL25A1) , substance dependence