Annual Meeting of the ADHD Molecular Genetics Network

我们建议继续一项为期多年的会议拨款，为研究人员提供一个论坛，以开展注意力缺陷多动障碍(ADHD)的分子遗传学合作研究。最初的应用是为了响应NIMH的呼吁，要求研究人员建立合作机制，以便于检测易患精神疾病的基因。ADHD是一种常见的儿童障碍，与学业失败、精神共病和心理社会残疾有关。由于家庭和双胞胎研究表明ADHD有很大的遗传成分，几个研究小组一直在进行这种疾病的分子遗传学研究。这些研究已经产生了几个荟萃分析结果，表明DRD4、DAT1、DRD5、SNAP-25和5HT1b基因与ADHD的病因有关。 尽管这些发现耐人寻味，但它们并没有带来新的治疗途径。由于全基因组的连锁研究一直是模棱两可的，而且对938个ADHD三联体的全基因组关联扫描没有发现全基因组的显著关联，因此ADHD的易感基因对个体的影响肯定很小。因此，发现ADHD的重复关联将需要大量样本和合作努力。协作策略在治疗糖尿病、克罗恩病和其他复杂疾病方面取得了成功，但它们需要非常大的样本。 尽管需要协作，但协作可能很困难。许多研究人员担心，大型合作研究将冲淡他们工作的科学影响，并使初级研究人员难以建立独立的声誉。此外，当考虑合作时，他们经常面临无法逾越的障碍。例如，每个地点的临床传统经常在哪些诊断工具适合使用方面发生冲突。这会导致创建不容易相互组合的数据集。尽管我们已开始在以往的会议上解决其中许多问题，但我们需要继续开展这一系列工作，以巩固这些成就，并完成以往各次会议中制定的协作计划。

We are proposing to continue a multi-year conference grant that has provided a forum for researchers to pursue collaborative studies of the molecular genetics of attention deficit hyperactivity disorder (ADHD). The original application was conceived in response to a call from the NIMH for researchers to establish mechanisms for collaborating in a manner that would facilitate the detection of genes predisposing to psychiatric disorders. ADHD is a common disorder of childhood associated with school failure, psychiatric comorbidity and psychosocial disability. Because family and twin studies suggest that ADHD has a substantial genetic component, several research groups have been pursuing molecular genetic studies of the disorder. These studies have already produced several meta-analytic findings implicating the DRD4, DAT1, DRD5, SNAP-25, and 5HT1B genes in the etiology of ADHD. Although these findings are intriguing, they have not led to new pathways for treatment. Because genomewide linkage studies have been equivocal and a genomewide association scan of 938 ADHD trios found no genomewide significant associations, susceptibility genes for ADHD must, individually, have very small effects. Thus, discovering replicated associations for ADHD will require large samples and collaborative efforts. Collaborative strategies have been successful for diabetes, Crohn's disease and other complex disorders, but they required very large samples. Despite the need for collaboration, collaboration can be difficult. Many investigators are concerned that large collaborative studies will dilute the scientific impact of their work and will make it difficult for junior investigators to establish independent reputations. Moreover, when collaborations are considered, they frequently face hurdles that cannot be surmounted. For example, clinical traditions at each site often clash regarding what diagnostic instruments are appropriate for use. This leads to the creation of data sets that are not easily combined with one another. Although we have begun to work out many of these issues at prior conferences, we need to continue the series to build upon those achievements and to complete the collaborative plans laid out in prior conferences.