Gizer Ian R, Ficks Courtney, Waldman Irwin D
Department of Genetics, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Room 5015 Genetic Medicine Building CB 7264, Chapel Hill, NC 27599-7264, USA.
Hum Genet. 2009 Jul;126(1):51-90. doi: 10.1007/s00439-009-0694-x. Epub 2009 Jun 9.
Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.
定量遗传学研究（即双胞胎和收养研究）表明，遗传因素在注意力缺陷多动障碍（ADHD）的发展中起了很大作用。在过去15年里，人们付出了巨大努力来确定与该疾病病因相关的基因，这导致了大量关于ADHD候选基因关联的文献，且这些文献往往相互矛盾。本研究的首要目标是对这些文献进行全面的荟萃分析综述，以确定哪些候选基因在各项研究中均显示出与儿童ADHD存在一致的关联证据。第二个目标是检验各候选基因效应大小在不同研究中的异质性，因为其存在可能表明存在调节变量，这些变量可以解释结果的不一致性。研究发现了几个与ADHD存在显著关联的候选基因，包括DAT1、DRD4、DRD5、5HTT、HTR1B和SNAP25。此外，还观察到ADHD与DAT1、DRD4、DRD5、DBH、ADRA2A、5HTT、TPH2、MAOA和SNAP25之间的关联存在显著异质性，这表明未来的研究应探索这些关联的潜在调节因素（例如，ADHD亚型诊断、性别、暴露于环境风险因素）。我们最后讨论了这些发现与ADHD遗传学未来研究相关的新兴主题之间的关系。
