Genomewide linkage scan for opioid dependence and related traits.
paper
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- Authors
- Gelernter, Joel; Panhuysen, Carolien; Wilcox, Marsha; Hesselbrock, Victor; Rounsaville, Bruce; Poling, James; Weiss, Roger; Sonne, Susan; Zhao, Hongyu; Farrer, Lindsay; Kranzler, Henry R
- Year
- 2006
- Journal
- American journal of human genetics
- PMID
- 16642432
- DOI
- 10.1086/503631
- PMCID
- PMC1474044
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).
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