Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies
Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies
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DOI：
10.1016/j.drugalcdep.2007.08.007
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Hasin, Deborah
中科院分区：
文献类型：
--
作者：
Heiman, Gary A.;Ogburn, Elizabeth;Hasin, Deborah
一些双胞胎研究表明，物质的启动和依赖是一个复杂的两阶段过程的一部分，一些遗传影响是特定阶段的，作用于从禁欲到启动的转变，或作用于从使用到依赖的转变。然而，关于两阶段模式仍然存在疑问，特别是对于非法药物。使用家族聚集设计，我们在一个具有全国代表性的大样本中测试了假设的对非法物质和酒精依赖的两阶段模型。药物或酒精问题的家族史与不会发展为依赖的入会(即有条件入会)密切相关。此外，药物或酒精问题的家族史与依赖显著相关，即使在对影响启蒙的因素(即条件性依赖)进行条件制约之后也是如此。这些结果表明，物质的启动和依赖至少部分涉及不同的家庭因素。不同的遗传因素影响启动和依赖的可能性对病例对照遗传关联研究中的控制组选择具有重要意义，并可能解释药物依赖的一些不一致的结果。如果一些遗传因素是特定阶段的(即，在启动和依赖中并不常见)，将戒断者纳入控制组可能会将启动的遗传效应与过渡到依赖的遗传效应混合在一起，提供不清楚的结果。根据关于遗传效应性质的具体问题(无论是启动、依赖，还是两者兼而有之)，设计病例对照遗传关联研究的调查人员应仔细考虑对照组的纳入和排除标准。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Some twin studies suggest that substance initiation and dependence are part of a complex, two-stage process and that some genetic influences are stage-specific, acting on either the transition from abstinence to initiation, or on the transition from use to dependence. However, questions remain about the two-stage model, especially for illicit drugs. Using a familial aggregation design, we tested the hypothesized two-stage model of dependence on illicit substances and alcohol in a large, nationally representative sample. Family history of drug or alcohol problems is significantly associated with initiation that does not progress to dependence (i.e., conditional initiation). Furthermore, family history of drug or alcohol problems is significantly associated with dependence even after conditioning on factors influencing initiation (i.e., conditional dependence). These results suggest that substance initiation and dependence involve at least partially distinct familial factors. The possibility that different genetic factors affect initiation and dependence has important implications for control group selection in case-control genetic association studies, and may explain some inconsistent results for drug dependence. If some genetic factors are stage-specific (i.e., not common across initiation and dependence), inclusion of abstainers in the control group may mix the genetic effects for initiation with those for transition to dependence, providing unclear results. Depending on the specific question about the nature of the genetic effect (whether on initiation, on dependence, or both), investigators designing case-control genetic association studies should carefully consider inclusion and exclusion criteria of the control group. (c) 2007 Elsevier Ireland Ltd. All rights reserved.