Weafer Jessica, Gray Joshua C, Hernandez Kyle, Palmer Abraham A, MacKillop James, de Wit Harriet
Department of Psychiatry and Behavioral Neuroscience, University of Chicago.
Department of Psychology, University of Georgia.
Exp Clin Psychopharmacol. 2017 Dec;25(6):512-520. doi: 10.1037/pha0000156.
Poor inhibitory control is a known risk factor for substance use disorders, making it a priority to identify the determinants of these deficits. The aim of the current study was to identify genetic associations with inhibitory control using the stop signal task in a large sample (n = 934) of healthy young adults of European ancestry. We genotyped the subjects genome-wide and then used a hierarchical approach in which we tested seven a priori single nucleotide polymorphisms (SNPs) previously associated with stop signal task performance, approximately 9,000 SNPs designated as high-value addiction (HVA) markers by the SmokeScreen array, and approximately five million genotyped and imputed SNPs, followed by a gene-based association analysis using the resultant p values. A priori SNP analyses revealed nominally significant associations between response inhibition and one locus in HTR2A (rs6313; p = .04, dominance model, uncorrected) in the same direction as prior findings. A nominally significant association was also found in one locus in ANKK1 (rs1800497; p = .03, uncorrected), although in the opposite direction of previous reports. After accounting for multiple comparisons, the HVA, genome-wide, and gene-based analyses yielded no significant findings. This study implicates variation in serotonergic and dopaminergic genes while underscoring the difficulty of detecting the influence of individual SNPs, even when biological information is used to prioritize testing. Although such small effect sizes suggest limited utility of individual SNPs in predicting risk for addiction or other impulse control disorders, they may nonetheless shed light on complex biological processes underlying poor inhibitory control. (PsycINFO Database Record
抑制控制能力差是物质使用障碍的一个已知风险因素，因此确定这些缺陷的决定因素成为当务之急。本研究的目的是在一个由欧洲血统的健康年轻成年人组成的大样本（n = 934）中，使用停止信号任务来确定与抑制控制相关的基因关联。我们对受试者进行了全基因组基因分型，然后采用分层方法，先测试了7个先前与停止信号任务表现相关的先验单核苷酸多态性（SNP），大约9000个被SmokeScreen阵列指定为高价值成瘾（HVA）标记的SNP，以及大约500万个基因分型和推算的SNP，随后使用所得p值进行基于基因的关联分析。先验SNP分析显示，反应抑制与5-羟色胺受体2A（HTR2A）中的一个位点（rs6313；p = 0.04，显性模型，未校正）之间存在名义上显著的关联，其方向与先前的研究结果一致。在ANKK1基因的一个位点（rs1800497；p = 0.03，未校正）也发现了名义上显著的关联，尽管其方向与先前的报告相反。在考虑了多重比较后，HVA、全基因组和基于基因的分析均未得出显著结果。这项研究表明了血清素能和多巴胺能基因的变异，同时强调了检测单个SNP影响的困难，即使利用生物学信息来优先进行检测。尽管如此小的效应大小表明单个SNP在预测成瘾或其他冲动控制障碍风险方面的效用有限，但它们仍可能有助于揭示抑制控制能力差背后的复杂生物学过程。（PsycINFO数据库记录）
