title: A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence.
abstract: 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).
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, CO 80309-0447, USA. michael.stallings@colorado.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stallings
authors.forename: Robin P
authors.initials: RP
authors.lastname: Corley
authors.forename: John K
authors.initials: JK
authors.lastname: Hewitt
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Krauter
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lessem
authors.forename: Susan K
authors.initials: SK
authors.lastname: Mikulich
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Rhee
authors.forename: Andrew
authors.initials: A
authors.lastname: Smolen
authors.forename: Susan E
authors.initials: SE
authors.lastname: Young
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Crowley
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003120:Colorado / Q000453:epidemiology; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D040641:Quantitative Trait Loci; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*