Buckland Paul R
Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff, UK.
Addiction. 2008 Nov;103(11):1768-76. doi: 10.1111/j.1360-0443.2008.02285.x. Epub 2008 Aug 14.
To assess the likelihood of finding genes which predispose to addiction and to present this information in a form accessible to the general readership of Addiction.
Review of the evidence that genetic factors play a significant role in the process of addiction and the proximity of the identification of these factors.
The search for the genetic susceptibility variants for many complex illnesses has been ongoing for decades, with increased pace in the last 20 years. However, until very recently only a small number of such variants have been found. Recent studies have used several thousand samples in genome-wide association studies and the latest genotyping technology and have reported a growing number of successes, but have highlighted the need for even larger samples and new statistical methods or new experimental approaches to identify fully the genes involved in the disease process. The phenotype for addiction to drugs is not well defined, and the heritability of addiction to drugs of abuse is far from clear and may be small compared to that of many other complex disorders. The absolute requirement for the administration of drugs before addiction can occur, and other environmental factors known to have a major effect, makes the selection of both probands and controls challenging for genetic studies. Many candidate genes put forward so far as susceptibility genes may be unrelated to the underlying process referred to as addiction but, rather, are related to the propensity to take drugs in the first place.
It is the underlying biological process which changes to an alternative state following addiction, which is the target of investigation, and it is not clear that even genome-wide association studies with sample sizes a magnitude greater than those reported so far would identify the genes involved which have the largest effect. Ultimately, modern neurobiological approaches may identify this process and the genes involved, and even at this stage identifying the susceptibility variants will require both biological as well as genetic analysis.
评估发现易成瘾基因的可能性，并以《成瘾》普通读者可理解的形式呈现这些信息。
回顾遗传因素在成瘾过程中起重要作用的证据以及这些因素识别的进展情况。
对许多复杂疾病的遗传易感性变异的研究已经进行了数十年，在过去20年中速度加快。然而，直到最近才发现少数此类变异。最近的研究在全基因组关联研究中使用了数千个样本以及最新的基因分型技术，并报告了越来越多的成功案例，但也强调需要更大的样本以及新的统计方法或新的实验方法来全面识别参与疾病过程的基因。药物成瘾的表型定义不明确，与许多其他复杂疾病相比，药物滥用成瘾的遗传度远不清楚且可能较小。成瘾发生前对药物给药的绝对要求以及已知有重大影响的其他环境因素，使得遗传研究中先证者和对照的选择都具有挑战性。迄今为止提出的许多作为易感基因的候选基因可能与所谓成瘾的潜在过程无关，而是与首先使用药物的倾向有关。
成瘾后转变为另一种状态的潜在生物学过程才是研究的目标，目前尚不清楚即使样本量比迄今报道的大一个数量级的全基因组关联研究是否能识别出影响最大的相关基因。最终，现代神经生物学方法可能会识别这个过程及相关基因，即使在现阶段识别易感变异也需要生物学以及遗传学分析。
