Kim J W, Biederman J, McGrath C L, Doyle A E, Mick E, Fagerness J, Purcell S, Smoller J W, Sklar P, Faraone S V
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Mol Psychiatry. 2008 Jun;13(6):624-30. doi: 10.1038/sj.mp.4002090. Epub 2007 Sep 18.
The norepinephrine transporter (NET) gene is an attractive candidate gene for attention-deficit hyperactivity disorder (ADHD). Noradrenergic systems are critical to higher brain functions such as attention and executive function, which are defective in ADHD. The clinical efficacy of medications that target NET also supports its role in the etiology of ADHD. Here, we have applied a dense mapping strategy to capture all genetic variations within the NET gene in a large number of ADHD families (474 trios). As a result, we found association of the same alleles from two single-nucleotide polymorphisms (rs3785143 and rs11568324) previously identified in another large-scale ADHD genetic study (International Multisite ADHD Geneproject). Furthermore, the effect sizes were consistent across both studies. This is the first time that identical alleles of NET from different studies were implicated, and thus our report provides further evidence that the NET gene is involved in the etiology of ADHD.
去甲肾上腺素转运体（NET）基因是注意力缺陷多动障碍（ADHD）一个颇具吸引力的候选基因。去甲肾上腺素能系统对于诸如注意力和执行功能等高级脑功能至关重要，而这些功能在ADHD中存在缺陷。针对NET的药物的临床疗效也支持其在ADHD病因学中的作用。在此，我们应用了一种密集图谱策略来捕获大量ADHD家系（474个三联体）中NET基因内的所有遗传变异。结果，我们发现了先前在另一项大规模ADHD基因研究（国际多中心ADHD基因项目）中鉴定出的两个单核苷酸多态性（rs3785143和rs11568324）的相同等位基因之间存在关联。此外，两项研究的效应大小是一致的。这是首次不同研究中涉及NET的相同等位基因，因此我们的报告提供了进一步证据表明NET基因参与ADHD的病因学。
