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


OBJECTIVE
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.


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


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
These results provide the first evidence of a potential molecular genetic basis for the comorbidity between DV and antisocial behavior.
Stallings
Michael C
MC
Institute for Behavioral Genetics and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, 80309-0444, USA. Michael.Stallings@Colorado.edu
Corley
Robin P
RP
Dennehey
Briana
B
Hewitt
John K
JK
Krauter
Kenneth S
KS
Lessem
Jeffrey M
JM
Mikulich-Gilbertson
Susan K
SK
Rhee
Soo Hyun
SH
Smolen
Andrew
A
Young
Susan E
SE
Crowley
Thomas J
TJ
D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology; D000328:Adult; D000987:Antisocial Personality Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D002874:Chromosome Mapping / Q000379:methods*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015897:Comorbidity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D016678:Genome; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D010641:Phenotype; D015995:Prevalence; D040641:Quantitative Trait Loci / Q000235:genetics*; D012044:Regression Analysis; D035781:Siblings / Q000523:psychology; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology