State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Addict Biol. 2012 Mar;17(2):479-89. doi: 10.1111/j.1369-1600.2011.00348.x. Epub 2011 Aug 4.
Alcohol use is highly heritable and has been associated with many gene variants, including those related to dopamine (DA). However, single gene association studies have shown inconsistent and small effects. Using a system-level approach, the current study aimed to estimate the overall effect of genetic variations in the DA system on alcohol use among male drinkers. One hundred seventy-six male college students who reported to have ever drunk alcohol were enrolled. Alcohol use was measured using the Alcohol Use Disorders Identification Test. Ninety-eight representative polymorphisms in all major DA neurotransmitter genes were genotyped. Using analysis of variance, we identified six single-nucleotide polymorphisms (SNP)s that made statistically significant contributions to alcohol use. Next, main effects and interactions of these SNPs were assessed using multiple regression. The final model accounted for approximately 20% of the variance for alcohol use. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be low, p ranging from 0.024 to 0.048. These results confirmed that DA-related gene variants made strong contributions to reported alcohol use and suggest that multiple regression can be a promising way to explore the genetic basis for multi-gene-determined human behaviors.
饮酒行为具有高度遗传性，与许多基因变异有关，包括与多巴胺（DA）相关的基因变异。然而，单一基因关联研究显示出不一致和较小的影响。本研究采用系统水平的方法，旨在估计 DA 系统中的遗传变异对男性饮酒者饮酒行为的总体影响。招募了 176 名报告曾经饮酒的男性大学生。使用酒精使用障碍识别测试来衡量饮酒行为。对所有主要 DA 神经递质基因中的 98 个代表性多态性进行了基因分型。通过方差分析，我们确定了六个对饮酒行为有统计学显著贡献的单核苷酸多态性（SNP）。接下来，使用多元回归评估了这些 SNP 的主效应和相互作用。最终模型解释了饮酒行为约 20%的变异。最后，通过置换分析确定了这些发现的概率很低，p 值范围为 0.024 至 0.048。这些结果证实，与 DA 相关的基因变异对报告的饮酒行为有很大贡献，并表明多元回归可能是探索多基因决定的人类行为遗传基础的一种很有前途的方法。
