Genomewide linkage scan for opioid dependence and related traits.
Risk of opioid dependence is genetically influenced. We recruited a sample of 393 small nuclear families (including 250 full-sib and 46 half-sib pairs), each with at least one individual with opioid dependence. Subjects underwent a detailed evaluation of substance dependence-related traits. As planned a priori to reduce heterogeneity, we used cluster analytic methods to identify opioid dependence-related symptom clusters, which were shown to be heritable. We then completed a genomewide linkage scan (with 409 markers) for the opioid-dependence diagnosis and for the two cluster-defined phenotypes represented by >250 families: the heavy-opioid-use cluster and the non-opioid-use cluster. Further exploratory analyses were completed for the other cluster-defined phenotypes. The statistically strongest results were seen with the cluster-defined traits. For the heavy-opioid-use cluster, we observed a LOD score of 3.06 on chromosome 17 (empirical pointwise P = .0002) for European American (EA) and African American (AA) subjects combined, and, for the non-opioid-use cluster, we observed a LOD score of 3.46 elsewhere on chromosome 17 (empirical pointwise P = .00002, uncorrected for multiple traits studied) for EA subjects only. We also identified a possible linkage (LOD score 2.43) of opioid dependence with chromosome 2 markers for the AA subjects. These results are an initial step in identifying genes for opioid dependence on the basis of a genomewide investigation (i.e., a study not conditioned on prior physiological candidate-gene hypotheses).
Gelernter
Joel
J
Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven; VA Connecticut Healthcare Center, West Haven. Electronic address: joel.gelernter@yale.edu.
Panhuysen
Carolien
C
Genetics Program, Department of Medicine, Boston University School of Medicine, Boston; Department of Biostatistics, School of Public Health, Boston University School of Medicine, Boston.
Wilcox
Marsha
M
Genetics Program, Department of Medicine, Boston University School of Medicine, Boston; Department of Biostatistics, School of Public Health, Boston University School of Medicine, Boston.
Hesselbrock
Victor
V
Department of Psychiatry, University of Connecticut School of Medicine, Farmington.
Rounsaville
Bruce
B
Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven; VA Connecticut Healthcare Center, West Haven.
Poling
James
J
Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven; VA Connecticut Healthcare Center, West Haven.
Weiss
Roger
R
Department of Psychiatry, Harvard Medical School, Boston; Alcohol and Drug Abuse Treatment Program, McLean Hospital, Belmont, MA.
Sonne
Susan
S
Department of Psychiatry, Medical University of South Carolina, Charleston.
Zhao
Hongyu
H
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven; Department of Genetics, Yale University School of Medicine, New Haven.
Farrer
Lindsay
L
Genetics Program, Department of Medicine, Boston University School of Medicine, Boston; Department of Biostatistics, School of Public Health, Boston University School of Medicine, Boston.
Kranzler
Henry R
HR
Department of Psychiatry, University of Connecticut School of Medicine, Farmington.
D000328:Adult; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D016000:Cluster Analysis; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D009679:Nuclear Family; D009293:Opioid-Related Disorders / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci; D018709:Statistics, Nonparametric