Fliers, E. A., Vasquez, A. A., Poelmans, G., Rommelse, N. N. J., Altink, M. E., Buschgens, C. J. M., Asherson, P., Banaschewski, T., Ebstein, R.P., Gill, M., Miranda, A., Mulas, F., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke, E. J. S.; Steinhausen, H-C., Faraone, S. V., Buitelaar, J. K., & Franke, B.

(2012) Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function. World Journal of Biological Psychiatry, DOI: 10.3109/15622975.2011.560279. [Request a copy] . View Article

Introduction: Motor coordination problems are frequent in children with ADHD. -- We performed the first genome-wide association study (GWAS) 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 IMAGE study were evaluated with the Parental Account of Children's Symptoms (PACS). Genetic association testing was performed in PLINK on 890 probands with genome-wide genotyping data. (Use of Perlegen Sciences genotyping platform of c. 600,000 tagging SNPs designed to be in high linkage disequilibrium with untyped SNPs for the HapMap populations.) 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:
1 - Although none of the findings reached genome-wide significance, bioinformatics analysis of the top-ranked findings revealed enrichment of genes involved in motor neuropathy & Amyotrophic Lateral-Sclerosis (ALS).

2 - Genes involved in neurite outgrowth & basic muscle function were also enriched.

3 - Among the highest ranked genes were MAP2K5, involved in Restless Legs Syndrome, & CHD6, causing motor coordination problems in mice.

4 - Further characterization of the top-ranked findings using DCD-Q subscales found nominal association for 15 SNPs.

5 - and, 6 genes containing at least one SNP with associations significant at p<10-5 level (i.e. MAP2K5, SLC7A2, ADCY2, TCF7L1, WDFY3, FLCN).

Discussion: Our findings provide clues about the etiology of motor coordination problems, but replication studies in independent samples are necessary.