The Association with Quantitative Response to Attention-Deficit/Hyperactivity Disorder Medication of the Previously Identified Neurodevelopmental Network Genes
The Association with Quantitative Response to Attention-Deficit/Hyperactivity Disorder Medication of the Previously Identified Neurodevelopmental Network Genes
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先前确定的神经发育网络基因与注意力缺陷/多动症药物定量反应的关联
DOI：
10.1089/cap.2018.0164
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发表时间：
2020
影响因子：
1.9
通讯作者：
Li Yang
中科院分区：
文献类型：
--
作者：
Yuanxin Zhong;Binrang Yang;Yi Su;Ying Qian;Qingjiu Cao;Suhua Chang;Yufeng Wang;Li Yang
目的：最近的药物影像学研究表明哌甲酯（MPH）和托莫西汀（ATX）治疗注意缺陷多动障碍（ADHD）可能具有共同的机制。以前的药物遗传学研究基本上只涉及神经递质系统中的基因，其差异非常小。因此，本研究的目的是调查是否在以前的ADHD病因全基因组关联研究（GWAS）中确定的神经发育基因可以预测患者的反应MPH和ATX，鉴于上述mechanisms of action.Methods：对于我们的样本241例ADHD患者，我们评估了ADHD评定量表（ADHD-RS）总症状评分从基线到第12周末的变化与MPH或ATX治疗。我们进行了关联分析，在遗传单标记，基因为基础的，集为基础的，和GWAS为基础的多基因levels.Results：在我们的分析中，无论是单核苷酸多态性（SNP），也没有基因水平的分析产生显着的标记与ADHD-RS评分的变化后，多重比较校正。多基因风险评分模型基于中国汉族GWAS中与ADHD病因学相关的SNPs（p ≤ 0.0001），预测ADHD药物治疗后症状改善（p= 0.018，R2 = 0.023）。
Objective:A recent pharmacoimaging study suggested that methylphenidate (MPH) and atomoxetine (ATX) might have common mechanisms for the treatment of attention-deficit/hyperactivity disorder (ADHD). Previous pharmacogenetic studies have by and large only involved genes in neurotransmitter systems, which accounted for very small variances. Therefore, this study aimed to investigate whether the neurodevelopmental genes identified in a prior ADHD etiology Genome-Wide Association Study (GWAS) could predict patients' responses to MPH and ATX, given the aforementioned mechanisms of action.Methods:For our sample of 241 patients with ADHD, we assessed the change in the ADHD rating scale (ADHD-RS) total symptom scores from baseline to the end of the 12th week of treatment with either MPH or ATX. We performed association analyses at the genetic single-marker, gene-based, set-based, and GWAS-based polygenic levels.Results:In our analyses, neither single nucleotide polymorphism (SNP) nor gene-level analyses yielded significant markers associated with the change in the ADHD-RS score after multiple comparison correction. The polygenic risk score model, which was based on SNPs associated with ADHD etiology at a threshold ofp≤ 0.0001 in a recent Han Chinese GWAS, predicted symptomatic improvement with ADHD medication (p= 0.018,R2= 0.023).Conclusion:Our results provide new evidence for a small influence of neurodevelopmental genes on the efficacy of medications for ADHD.