Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci.
Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci.
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经常赌徒延迟打折的遗传基础：对先验候选者的检查和探索一组与多巴胺相关的基因座。
DOI：
10.1002/brb3.284
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发表时间：
2014
影响因子：
3.1
通讯作者：
MacKillop, James
中科院分区：
文献类型：
--
作者：
Gray, Joshua C.;MacKillop, James
延迟折扣是冲动性的行为经济指数，反映了相对于较大的延迟奖励而言对较小的即时奖励的偏好。它一直与病理性赌博和其他形式的成瘾行为相关，并且被认为是一种可能将遗传变异和成瘾性疾病风险（即内表型）联系起来的行为特征。迄今为止的研究已经揭示了与多巴胺神经传递相关的多态性的显着关联。当前的研究在经常赌徒的样本中检查了延迟折扣与先前关联的变异和一组新的多巴胺相关变异之间的关联。参与者是 175 名欧洲血统的每周赌徒，他们完成了货币选择问卷以评估延迟折扣偏好，并通过唾液提供了 DNA。在先验测试中，先前与延迟奖励折扣相关的两个基因座（rs1800497和rs4680）没有被复制，然而，DRD4 VNTR的长形式与延迟奖励的较低折扣显着相关。对多巴胺相关组的探索性分析揭示了与多巴胺合成、分解、再摄取和受体功能相关的基因（DRD3、SLC6A3、DDC、DBH 和 SLC18A2）中另外 11 个显着关联。名义上显着基因座的总遗传风险评分占贴现方差的 17%。中介分析在很大程度上支持相关位点、延迟贴现和病态赌博严重程度之间存在间接影响。这些发现并没有复制之前报道的关联，而是确定了几种新的候选者，并为系统生物学方法提供初步支持，以了解延迟贴现的遗传基础。
Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine-related variants in a sample of frequent gamblers. Participants were 175 weekly gamblers of European ancestry who completed the Monetary Choice Questionnaire to assess delay discounting preferences and provided a DNA via saliva. In a priori tests, two loci previously associated with delayed reward discounting (rs1800497 and rs4680) were not replicated, however, the long form of DRD4 VNTR was significantly associated with lower discounting of delayed rewards. Exploratory analysis of the dopamine-related panel revealed 11 additional significant associations in genes associated with dopamine synthesis, breakdown, reuptake, and receptor function (DRD3, SLC6A3, DDC, DBH, and SLC18A2). An aggregate genetic risk score from the nominally significant loci accounted for 17% of the variance in discounting. Mediational analyses largely supported the presence of indirect effects between the associated loci, delay discounting, and pathological gambling severity. These findings do not replicate previously reported associations but identify several novel candidates and provide preliminary support for a systems biology approach to understand the genetic basis of delay discounting.
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影响因子：
3.7
作者：
Caporaso N;Gu F;Chatterjee N;Sheng-Chih J;Yu K;Yeager M;Chen C;Jacobs K;Wheeler W;Landi MT;Ziegler RG;Hunter DJ;Chanock S;Hankinson S;Kraft P;Bergen AW
通讯作者：
Bergen AW
影响因子：
5.3
作者：
Isles, AR;Humby, T;Wilkinson, LS
通讯作者：
Wilkinson, LS
影响因子：
3.4
作者：
MacKillop, James;Amlung, Michael T.;Few, Lauren R.;Ray, Lara A.;Sweet, Lawrence H.;Munafo, Marcus R.
通讯作者：
Munafo, Marcus R.
DOI：
10.1002/ajmg.b.30876
发表时间：
2008-12-05
影响因子：
2.8
作者：
Kollins, S. H.;Anastopoulos, A. D.;Ashley-Koch, A. E.
通讯作者：
Ashley-Koch, A. E.
影响因子：
25
作者：
Kreek, MJ;Nielsen, DA;LaForge, KS
通讯作者：
LaForge, KS