期刊
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
卷 13, 期 3, 页码 211-222出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/15622975.2011.560279
关键词
Motor coordination problems; ADHD; genome-wide association study (GWAS); neurite outgrowth; skeletal muscle function
类别
资金
- NIH [R01MH081803, R01MH62873]
- Netherlands Scientific Organization (NWO) [480-05-003]
- Shire
- Janssen-Cilag
- Lilly
- Janssen McNeil
- Medice
- Novartis
- UCB
- German Research Society
- Schwaabe
- Flynn
- Qbtech
- Eli Lilly
- Swedish Orphan International
- McNeil Pediatrics
- Eli Lilly Company
- National Institute of Mental Health
- National Institute of Child Health and Development
- National Institute of Neurological Diseases and Stroke
- Medical Research Council [G9817803B] Funding Source: researchfish
Objectives. 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. Methods. 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). Results. 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. Conclusions. Our findings provide clues about the aetiology of motor coordination problems, but replication studies in independent samples are necessary.
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