The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder:: association signals in DRD4, DAT1 and 16 other genes
The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder:: association signals in DRD4, DAT1 and 16 other genes
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DOI：
10.1038/sj.mp.4001869
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发表时间：
2006-10-01
影响因子：
11
通讯作者：
Johansson, L.
中科院分区：
文献类型：
--
作者：
Brookes, K.;Xu, X.;Johansson, L.
注意缺陷多动障碍（ADHD）是一种常见的神经发育障碍，多数病例始于儿童早期并持续到成年。家庭和双胞胎研究已证明了遗传因素的重要性，候选基因关联研究也已确定了几个对ADHD有微小但显著影响的基因位点。为了进一步阐明已报道的关联并确定新的相关基因，我们检测了1038个单核苷酸多态性（SNP），这些SNP涵盖51个参与神经递质通路（特别是多巴胺、去甲肾上腺素和血清素通路）调节的候选基因，以及昼夜节律基因。我们对国际多中心ADHD基因项目所确定的776例符合《精神障碍诊断与统计手册》第四版（DSM - IV）ADHD混合型的样本进行了家庭内关联测试分析。我们发现18个基因中的一个或多个SNP具有名义上的显著性，包括文献中两个重复率最高的发现：DRD4和DAT1。对每个基因中分析的SNP数量进行校正后的全基因测试确定了与TPH2、ARRB2、SYP、DAT1、ADRB2、HES1、MAOA和PNMT的关联。需要进一步的研究来证实或反驳所观察到的关联以及它们对其他样本的普遍性。
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.