Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Annu Rev Genomics Hum Genet. 2012;13:241-61. doi: 10.1146/annurev-genom-090711-163844. Epub 2012 Jun 11.
A large segment of the population suffers from addiction to alcohol, smoking, or illicit drugs. Not only do substance abuse and addiction pose a threat to health, but the consequences of addiction also impose a social and economic burden on families, communities, and nations. Genome-wide linkage and association studies have been used for addiction research with varying degrees of success. The most well-established genetic factors associated with alcohol dependence are in the genes encoding alcohol dehydrogenase (ADH), which oxidizes alcohol to acetaldehyde, and aldehyde dehydrogenase (ALDH2), which oxidizes acetaldehyde to acetate. Recently emerging genetic studies have linked variants in the genes encoding the α3, α5, and β4 nicotinic acetylcholine receptor subunits to smoking risk. However, the influence of these well-established genetic variants accounts for only a small portion of the heritability of alcohol and nicotine addiction, and it is likely that there are both common and rare risk variants yet to be identified. Newly developed DNA sequencing technologies could potentially advance the detection of rare variants with a larger impact on addiction risk.
很大一部分人患有酒精、吸烟或非法药物成瘾。药物滥用和成瘾不仅对健康构成威胁，而且成瘾的后果也给家庭、社区和国家带来社会和经济负担。全基因组连锁和关联研究已被用于成瘾研究，取得了不同程度的成功。与酒精依赖最相关的最成熟的遗传因素是编码将酒精氧化为乙醛的醇脱氢酶 (ADH) 和将乙醛氧化为乙酸盐的醛脱氢酶 (ALDH2) 的基因。最近出现的遗传研究将编码α3、α5 和β4 烟碱型乙酰胆碱受体亚基的基因中的变异与吸烟风险联系起来。然而，这些成熟的遗传变异仅占酒精和尼古丁成瘾遗传率的一小部分，很可能还有常见和罕见的风险变异有待发现。新开发的 DNA 测序技术有可能提高对成瘾风险有更大影响的罕见变异的检测能力。
