Fliers, Ellen A.; Vasquez, Alejandro Arias; Poelmans, Geert; Rommelse, Nanda N.J.; Altink, Marieke; Buschgens, Cathelijne; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard; Gill, Michael; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans- Christoph; Faraone, Stephen V.; Buitelaar, Jan K.; Franke, Barbara:

Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function

In: World Journal of Biological Psychiatry, (2011) ; Nr. 12
Zeitschriftenaufsatz / Fach: Medizin
Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters
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 functions
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.