Genomewide linkage scan for opioid dependence and related traits
Genomewide linkage scan for opioid dependence and related traits
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DOI：
10.1086/503631
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发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Kranzler, HR
中科院分区：
文献类型：
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作者：
Gelernter, J;Panhuysen, C;Kranzler, HR
阿片类药物依赖的风险受遗传影响。我们招募了393个小核心家庭（包括250个全同胞和46个半同胞对）的样本，每个家庭至少有一个阿片类药物依赖的个体。受试者进行了详细的评估物质依赖相关的特质。按照减少异质性的先验计划，我们使用聚类分析方法来识别阿片类药物依赖相关的症状群，这些症状群被证明是可遗传的。然后，我们完成了一个全基因组连锁扫描（有409个标记），用于阿片类药物依赖诊断和两个由超过250个家庭代表的聚类定义的表型：重度阿片类药物使用聚类和非阿片类药物使用聚类。对其他聚类定义的表型完成了进一步的探索性分析。统计学上最强的结果被视为与集群定义的性状。对于大量使用阿片类药物的集群，我们观察到欧洲裔美国人（EA）和非洲裔美国人（AA）受试者在17号染色体上的LOD评分为3.06（经验逐点P = .0002），对于非阿片类药物使用集群，我们观察到仅EA受试者在17号染色体其他地方的LOD评分为3.46（经验逐点，未校正研究的多个特征）。P = .00002我们还确定了阿片类药物依赖与AA受试者2号染色体标记物的可能联系（LOD评分2.43）。这些结果是基于全基因组研究（即，不以先前的生理学候选基因假设为条件的研究）。
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, uncorrected for multiple traits studied) for EA subjects only. P = .00002 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).