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.
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.
Authors: Joseph T Sakai; Thomas J Crowley; Michael C Stallings; Matthew McQueen; John K Hewitt; Christian Hopfer; Nicole R Hoft; Marissa A Ehringer Journal: Psychiatr Genet Date: 2012-04 Impact factor: 2.458
Authors: Whitney E Melroy; Sarah H Stephens; Joseph T Sakai; Helen M Kamens; Matthew B McQueen; Robin P Corley; Michael C Stallings; Christian J Hopfer; Kenneth S Krauter; Sandra A Brown; John K Hewitt; Marissa A Ehringer Journal: Behav Genet Date: 2014-04-01 Impact factor: 2.805
Authors: Joel Gelernter; Carolien Panhuysen; Marsha Wilcox; Victor Hesselbrock; Bruce Rounsaville; James Poling; Roger Weiss; Susan Sonne; Hongyu Zhao; Lindsay Farrer; Henry R Kranzler Journal: Am J Hum Genet Date: 2006-03-16 Impact factor: 11.025
Authors: Isabel R Schlaepfer; Nicole R Hoft; Allan C Collins; Robin P Corley; John K Hewitt; Christian J Hopfer; Jeffrey M Lessem; Matthew B McQueen; Soo Hyun Rhee; Marissa A Ehringer Journal: Biol Psychiatry Date: 2007-12-27 Impact factor: 13.382
Authors: K R Merikangas; K P Conway; J Swendsen; V Febo; L Dierker; W Brunetto; M Stolar; G Canino Journal: J Epidemiol Community Health Date: 2009-01-15 Impact factor: 3.710