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Arch Gen Psychiatry. 2005 Sep;62(9):1042-51.

A genome-wide search for quantitative trait Loci that influence antisocial drug dependence in adolescence.

Author information

1
Institute for Behavioral Genetics and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, 80309-0444, USA. Michael.Stallings@Colorado.edu

Abstract

BACKGROUND:

Among adolescents, externalizing problem behavior and substance use disorders are often comorbid. Familial influences, including shared genetic risk factors, may account for part of this comorbidity. Previously we reported 2 chromosomal regions (3q24-3q25 and 9q34) likely to contain genes that influence substance dependence vulnerability (DV) in adolescence.

OBJECTIVES:

To identify quantitative trait loci (QTLs) that influence externalizing problem behavior in adolescence and to determine whether any identified QTL overlap chromosomal regions that influence DV.

DESIGN:

Regression-based QTL mapping procedures designed for selected sibling pair samples.

SETTING:

Patient probands were drawn from consecutive admissions to residential and outpatient (milieu-type) treatment facilities for substance abuse and delinquency operated by the University of Colorado; most of these patients were referred for treatment by juvenile justice or social service agencies.

PATIENTS:

A total of 249 proband-sibling pairs from 191 families were selected for the study. Patient probands were 13 to 19 years of age; siblings of the probands ranged in age from 12 to 25 years.

MAIN OUTCOME MEASURES:

A community-based sample of 4493 adolescents and young adults was used to define clinically significant, heritable, age- and sex-normed indexes of DV, conduct disorder symptoms (CDS), and a composite index of antisocial substance dependence (DV + CDS). Siblings and parents were genotyped for 374 microsatellite markers distributed across the 22 autosomes (mean intermarker distance, 9.2 centimorgans).

RESULTS:

For both DV and CDS, there was evidence of linkage to the same region on chromosome 9q34, as well as to 3q24-3q25 for DV, and a novel region on chromosome 17q12 for CDS. Our composite index (DV + CDS) yielded the strongest evidence for linkage (logarithm of odds = 2.65) to the chromosome 9q34 region.

CONCLUSION:

These results provide the first evidence of a potential molecular genetic basis for the comorbidity between DV and antisocial behavior.

PMID:
16143736
DOI:
10.1001/archpsyc.62.9.1042
[Indexed for MEDLINE]

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