title: Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Fliers
authors.forename: Alejandro Arias
authors.initials: AA
authors.lastname: Vasquez
authors.forename: Geert
authors.initials: G
authors.lastname: Poelmans
authors.forename: Nanda
authors.initials: N
authors.lastname: Rommelse
authors.forename: Marieke
authors.initials: M
authors.lastname: Altink
authors.forename: Cathelijne
authors.initials: C
authors.lastname: Buschgens
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Richard
authors.initials: R
authors.lastname: Ebstein
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Ana
authors.initials: A
authors.lastname: Miranda
authors.forename: Fernando
authors.initials: F
authors.lastname: Mulas
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oades
authors.forename: Herbert
authors.initials: H
authors.lastname: Roeyers
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Joseph
authors.initials: J
authors.lastname: Sergeant
authors.forename: Edmund
authors.initials: E
authors.lastname: Sonuga-Barke
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Steinhausen
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D019957:Motor Skills Disorders / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011795:Surveys and Questionnaires