Sonuga-Barke Edmund J S, Brookes Keeley-Joanne, Buitelaar Jan, Anney Richard, Bitsakou Paraskevi, Baeyens Dieter, Buschgens Cathelijne, Chen Wai, Christiansen Hanna, Eisenberg Jacques, Kuntsi Jonna, Manor Iris, Meliá Amanda, Mulligan Aisling, Rommelse Nanda, Müller Ueli C, Uebel Henrik, Banaschewski Tobias, Ebstein Richard, Franke Barbara, Gill Michael, Miranda Ana, Oades Robert D, Roeyers Herbert, Rothenberger Aribert, Sergeant Joseph, Steinhausen Hans Christoph, Thompson Margaret, Taylor Eric, Asherson Philip, Faraone Stephen V
School of Psychology, University of Southampton, Southampton, UK.
Am J Med Genet B Neuropsychiatr Genet. 2008 Apr 5;147(3):316-9. doi: 10.1002/ajmg.b.30596.
A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD.
注意缺陷多动障碍（ADHD）基因研究的一个主要目标是识别可能有助于区分该疾病内在异质性的个体特征。[米尔等人（2006年）；《老年精神病学档案》63:462 - 469]最近报告了两种与多巴胺相关的风险多态性（外显子3中的多巴胺D4受体基因（DRD4）可变数目串联重复序列（VNTR）和3'非翻译区中的多巴胺转运体1基因（DAT1）VNTR）与ADHD患者智商降低之间可能存在重要关联。本研究的目的是在临床样本中重复[米尔等人（2006年）；《老年精神病学档案》63:462 - 469]的研究结果，并将分析扩展到最近一项研究[布鲁克斯等人（2006年）；《分子遗传学》11:934 - 953]中确定的一系列假定的ADHD风险等位基因的替代单核苷酸多态性（SNP）标记。参与者为1081名经研究确诊为合并型ADHD的儿童和青少年以及1300名未受影响的兄弟姐妹，他们参与了国际多中心ADHD遗传学（IMAGE）项目。他们是从欧洲各地的多个机构招募的：比利时、英国、德国、爱尔兰、以色列、荷兰、西班牙和瑞士。结果显示，ADHD与智商降低有关。然而，在先证者及其兄弟姐妹中，这两种与多巴胺相关的风险多态性与智商之间均无关联。此外，之前在该样本中已证明与ADHD相关的其他选定基因标记与智商无关。这项对临床确诊且经过严格诊断的样本进行的大规模研究未能重复多巴胺系统基因多态性与ADHD患者智商之间的关联。我们还观察到其他SNP与ADHD患者的智商无关联。
