The possible involvement of genetic variants of NET1 in the etiology of attention-deficit/hyperactivity disorder comorbid with oppositional defiant disorder.
The possible involvement of genetic variants of NET1 in the etiology of attention-deficit/hyperactivity disorder comorbid with oppositional defiant disorder.
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DOI：
10.1111/jcpp.12278
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Lu Liu;Jia Hua Cheng;Haimei Li;Li Yang;Q. Qian;Yufeng Wang
中科院分区：
文献类型：
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作者：
Lu Liu;Jia Hua Cheng;Haimei Li;Li Yang;Q. Qian;Yufeng Wang
背景注意力缺陷多动障碍（ADHD）和对立违抗性障碍（ODD）常常共存，并共享一些遗传影响。现有文献的证据表明，与ODD共病可能会增加ADHD的遗传异质性。本研究旨在探讨去甲肾上腺素转运体基因（NET 1）在ADHD和ODD共病中的作用。方法对1,815例ADHD患者（其中ODD 587例，占32.3%）的NET 1基因6个单核苷酸多态性（SNPs）进行基因分型。采用卡方检验进行假病例对照研究，比较ADHD伴和不伴ODD的等位基因和基因型分布。其中，有1，249名先证者与他们的父母组成三人组，使用传递不平衡检验（TDTs）进行以家庭为基础的关联研究。此外，1，337名ADHD先证者有ODD症状的详细信息，并使用协方差分析（ANCOVA）进行基因型定量分析。为了考虑其他合并症与ODD的重叠和相关性，并消除其潜在的混杂效应，我们在排除ODD以外的其他合并症后，对“纯ADHD+ODD”与“仅ADHD”进一步重复上述分析。结果假病例对照研究结果显示，在ADHD伴ODD组和不伴ODD组中，SNP rs3785143的等位基因和基因型分布存在差异。以家庭为基础的关联检验表明，rs3785143的T等位基因在ADHD与ODD三重的过度传递，但没有偏见的传输在那些没有ODD。协方差分析显示，rs3785143基因型与ADHD先证者的ODD症状相关，尤其是在控制了性别、年龄、临床亚型和智力因素后，与“争论/违抗行为（ADB）”维度相关。在排除其他合并症的样本后，上述相关性仍然存在。结论NET 1与ADHD先证者ODD和ODD症状的共病相关。我们的研究结果强调了在ADHD遗传学研究中考虑ODD共病的重要性，特别是ADHD与ADB。然而，仍需要在独立样本或不同群体中进一步重复。
BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) often coexist and shared some genetic influences. Evidence from the existing literature indicated that comorbid with ODD may increase the heterogeneity of ADHD genetics. Our present study sought to investigate the role of norepinephrine transporter gene (NET1) for ADHD comorbid with ODD. METHODS Six single nucleotide polymorphisms (SNPs) of NET1 were genotyped for a total of 1,815 ADHD cases, including 587 subjects (32.3%) with ODD. Chi-square tests were conducted for pseudo case-control study comparing allelic and genotypic distributions between ADHD with and without ODD. Among them, there were 1,249 probands together with their parents composing trios for family-based association studies using transmission disequilibrium tests (TDTs). In addition, 1,337 ADHD probands have detailed information of ODD symptoms and were included for quantitative analyses with genotypes using analyses of covariance (ANCOVA). To consider the overlap and correlation of other comorbidities with ODD and eliminate their potential confounding effect, we further repeated above analyses for 'pure ADHD+ODD' versus 'ADHD-only' after excluding other comorbidities except for ODD. RESULTS The pseudo case-control study showed different allelic and genotypic distributions of SNP rs3785143 between ADHD with ODD and those without ODD. Family-based association tests indicated overtransmission of the T allele of rs3785143 in ADHD with ODD trios, but no biased transmission in those without ODD. ANCOVA showed association between genotypes of rs3785143 with ODD symptoms in ADHD probands, especially with 'Argumentative/Defiant Behavior (ADB)' dimension after controlling gender, age, clinical subtypes and intelligence. Above association still existed after removing the samples with other comorbidities. CONCLUSION NET1 was associated with comorbidity of ODD and ODD symptoms in ADHD probands. Our findings emphasize the importance of considering the comorbidity of ODD in ADHD genetic studies, especially ADHD with ADB. However, further replication in independent sample or different populations is still needed.