Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
World J Biol Psychiatry. 2012 Mar;13(3):211-22. doi: 10.3109/15622975.2011.560279. Epub 2011 Apr 7.
Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD may identify a sample of reduced genetic heterogeneity.
Children with ADHD from the International Multicentre ADHD Genetic (IMAGE) study were evaluated with the Parental Account of Children's Symptoms. Genetic association testing was performed in PLINK on 890 probands with genome-wide genotyping data. Bioinformatics enrichment-analysis was performed on highly ranked findings. Further characterization of the findings was conducted in 313 Dutch IMAGE children using the Developmental Coordination Disorder Questionnaire (DCD-Q).
Although none of the findings reached genome-wide significance, bioinformatics analysis of the top-ranked findings revealed enrichment of genes for motor neuropathy and amyotrophic lateral sclerosis. Genes involved in neurite outgrowth and muscle function were also enriched. Among the highest ranked genes were MAP2K5, involved in restless legs syndrome, and CHD6, causing motor coordination problems in mice. Further characterization of these findings using DCD-Q subscales found nominal association for 15 SNPs.
Our findings provide clues about the aetiology of motor coordination problems, but replication studies in independent samples are necessary.
注意力缺陷/多动障碍（ADHD）儿童常存在运动协调问题。我们进行了一项全基因组关联研究，以确定导致运动协调问题的基因，假设 ADHD 儿童存在此类问题可能会确定遗传异质性降低的样本。
来自国际多中心 ADHD 遗传（IMAGE）研究的 ADHD 儿童使用父母对儿童症状的描述进行评估。在具有全基因组基因分型数据的 890 名先证者中，在 PLINK 中进行遗传关联测试。对高排名发现进行生物信息学富集分析。使用发育协调障碍问卷（DCD-Q）对 313 名荷兰 IMAGE 儿童进行进一步特征描述。
虽然没有发现达到全基因组显著性，但对排名最高的发现进行生物信息学分析表明，运动神经病和肌萎缩侧索硬化症相关基因富集。参与轴突生长和肌肉功能的基因也存在富集。排名最高的基因包括 MAP2K5，与不安腿综合征有关，以及 CHD6，导致小鼠运动协调问题。使用 DCD-Q 子量表进一步对这些发现进行特征描述，发现 15 个 SNP 存在名义关联。
我们的发现为运动协调问题的病因提供了线索，但需要在独立样本中进行复制研究。
