A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population
A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population
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DOI：
10.1038/sj.mp.4002139
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发表时间：
2009-05-01
影响因子：
11
通讯作者：
Wang, Y.
中科院分区：
文献类型：
--
作者：
Guan, L.;Wang, B.;Wang, Y.
注意缺陷多动障碍（ADHD）是一种常见的儿童期发病的行为障碍，具有明确的遗传因素。对ADHD易感基因的研究主要集中在参与单胺系统调节的基因上。在这项研究中，我们重点关注多巴胺、去甲肾上腺素和血清素神经传递各个方面的基因，并通过筛选中国汉族样本中 23 个候选基因的 245 个单核苷酸多态性 (SNP) 进行全面的关联分析。对总共 182 名 DSM-IV ADHD 儿童和 184 名健康对照进行了基因分型和分析，平均密度为每 6.1 kb 1 个 SNP。实施单 SNP 和多标记单倍型分析以利用 ADHD 及其诊断亚型的关联信号。经验 P 值是在 5000 次排列的基础上得出的，以评估全基因组的统计显着性。 MAOA 产生了与 ADHD 相关的高度提示性证据（经验 P < 0.01，OR = 1.94）。对于注意力不集中的 ADHD，MAOA、DDC 和 SYP 显示出相关性的暗示证据（经验 P < 0.05）。 ADRA2C 对 ADHD 合并型具有提示意义（经验 P < 0.05）。此外，对于 6 个基因（SNAP25、NET1、DBH、CHRNA4、DRD3 和 SYT1），我们检测到一个或多个具有名义 P 值的 SNP
Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset behavioral disorder with a definite genetic component. The search for genes predisposing to ADHD has focused on genes involved in the regulation of monoamine systems. In this study, we emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245 single-nucleotide polymorphisms (SNPs) of 23 candidate genes in a sample of Chinese Han descent. A total of 182 DSM-IV ADHD children and 184 healthy controls were genotyped and analyzed with an average density of one SNP every 6.1 kb. Both single-SNP and multi-marker haplotype analyses were implemented to exploit association signal for ADHD and its diagnostic subtypes. Empirical P-values were derived on the basis of 5000 permutations to evaluate gene-wide statistical significance. MAOA yielded highly suggestive evidence of association (empirical P < 0.01, OR = 1.94) with ADHD. For inattentive ADHD, MAOA, DDC and SYP showed suggestive evidence of association (empirical P < 0.05). ADRA2C achieved suggestive significance (empirical P < 0.05) for ADHD combined type. Additionally, for six genes (SNAP25, NET1, DBH, CHRNA4, DRD3 and SYT1) we detected one or more SNPs with nominal P-values