Lowe Naomi, Kirley Aiveen, Hawi Ziarih, Sham Pak, Wickham Harvey, Kratochvil Christopher J, Smith Shelley D, Lee Saretta Y, Levy Florence, Kent Lindsey, Middle Fiona, Rohde Luis A, Roman Tatiana, Tahir Eda, Yazgan Yanke, Asherson Philip, Mill Jonathan, Thapar Anita, Payton Antony, Todd Richard D, Stephens Timothy, Ebstein Richard P, Manor Iris, Barr Cathy L, Wigg Karen G, Sinke Richard J, Buitelaar Jan K, Smalley Susan L, Nelson Stan F, Biederman Joseph, Faraone Stephen V, Gill Michael
Department of Genetics, Trinity College, Dublin 2, Ireland.
Am J Hum Genet. 2004 Feb;74(2):348-56. doi: 10.1086/381561. Epub 2004 Jan 19.
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.
注意力缺陷多动障碍（ADHD）是一种具有高度遗传性的早发性异质性疾病，由注意力不集中、多动和冲动三联征组成。该疾病具有显著的遗传成分，病因学理论包括多巴胺能系统异常，其中DRD4、DAT1、SNAP25和DRD5被认为是主要的易感基因。最初有报道称ADHD与位于DRD5基因18.5 kb处的一个微卫星标记的常见148 bp等位基因存在关联，随后的几项研究显示与该等位基因的关联趋势不显著。为了确定（CA）（n）重复序列与ADHD的假定关联，我们收集了14个先证者及其父母的独立样本的基因型信息，分别进行分析，在不存在异质性的情况下，将它们作为一个联合样本进行分析。联合分析显示与DRD5基因座存在关联（P = 0.00005；优势比1.24；95%置信区间1.12 - 1.38）。这种关联似乎仅限于主要为注意力不集中型和混合型临床亚型。
