A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence

Drug Alcohol Depend. 2003 Jun 5;70(3):295-307. doi: 10.1016/s0376-8716(03)00031-0.


This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Colorado / epidemiology
  • Female
  • Genetic Linkage / genetics
  • Genome, Human*
  • Genotype
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Quantitative Trait Loci*
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / genetics*