Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
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DOI：
10.1038/s41588-018-0307-5
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发表时间：
2019-02-01
期刊：
影响因子：
30.8
通讯作者：
Stensland, Synne Oien
中科院分区：
文献类型：
--
作者：
Liu, Mengzhen;Jiang, Yu;Stensland, Synne Oien
烟草和酒精的使用是死亡的主要原因，影响许多复杂疾病和障碍的风险（1）。它们是遗传的（2，3）和病因相关的（4，5）行为，这些行为对基因发现的努力具有抵抗力（6-11）。在高达120万人的样本量中，我们在406个基因座中发现了566个遗传变异，这些基因座与烟草使用的多个阶段（开始、停止和重度）以及酒精使用相关，其中150个基因座证明了多效性关联。吸烟表型与许多健康状况呈正遗传相关，而饮酒与这些状况呈负相关，因此饮酒的遗传风险增加与较低的疾病风险相关。我们报告的证据表明，烟草和酒精的使用涉及许多系统，包括基因参与烟碱，多巴胺能和多巴胺能神经传递。这些结果提供了一个坚实的起点，以评估这些基因座在模式生物和更精确的物质使用措施的影响。
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders(1). They are heritable(2,3) and etiologically related(4,5) behaviors that have been resistant to gene discovery efforts(6-11). In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.