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Genetic variations in the dopaminergic system and alcohol use: A system-level analysis

机译：多巴胺能系统的遗传变异和饮酒：系统级分析

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摘要

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.
机译：酒精的使用具有高度的遗传性，并且与许多基因变异有关，包括与多巴胺（DA）有关的变异。但是，单基因关联研究显示出不一致且影响很小。使用系统级方法，当前研究旨在评估DA系统中遗传变异对男性饮酒者饮酒的总体影响。一百六十六名据报曾喝过酒的男大学生被录取。使用酒精使用障碍识别测试来测量酒精使用量。对所有主要DA神经递质基因中的98个代表性多态性进行基因分型。使用方差分析，我们确定了六个单核苷酸多态性（SNP），它们在饮酒方面具有统计学意义。接下来，使用多元回归评估了这些SNP的主要作用和相互作用。最终模型约占酒精使用差异的20％。最后，置换分析确定偶然获得这些发现的可能性很低，p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酒精使用做出了重要贡献，并表明多元回归可能是探索多基因决定的人类行为的遗传基础的有前途的方法。

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