title: Biological overlap of attention-deficit/hyperactivity disorder and autism spectrum disorder: evidence from copy number variants.
abstract: OBJECTIVE
  Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur and share genetic risks. The aim of this analysis was to determine more broadly whether ADHD and ASD share biological underpinnings.
  
  
  METHODS
  We compared copy number variant (CNV) data from 727 children with ADHD and 5,081 population controls to data from 996 individuals with ASD and an independent set of 1,287 controls. Using pathway analyses, we investigated whether CNVs observed in individuals with ADHD have an impact on genes in the same biological pathways as on those observed in individuals with ASD.
  
  
  RESULTS
  The results suggest that the biological pathways affected by CNVs in ADHD overlap with those affected by CNVs in ASD more than would be expected by chance. Moreover, this was true even when specific CNV regions common to both disorders were excluded from the analysis. After correction for multiple testing, genes involved in 3 biological processes (nicotinic acetylcholine receptor signalling pathway, cell division, and response to drug) showed significant enrichment for case CNV hits in the combined ADHD and ASD sample.
  
  
  CONCLUSIONS
  The results of this study indicate the presence of significant overlap of shared biological processes disrupted by large rare CNVs in children with these 2 neurodevelopmental conditions.
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK. Electronic address: martinjm1@cardiff.ac.uk.
authors: Joanna
authors: J
authors: Martin
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Miriam
authors: M
authors: Cooper
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Marian L
authors: ML
authors: Hamshere
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Andrew
authors: A
authors: Pocklington
authors: Hospital for Sick Children and University of Toronto, Ontario, Canada.
authors: Stephen W
authors: SW
authors: Scherer
authors: Bute Medical School, University of St. Andrews, Fife, Scotland.
authors: Lindsey
authors: L
authors: Kent
authors: Trinity Centre for Health Sciences, Dublin, Ireland.
authors: Michael
authors: M
authors: Gill
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Michael J
authors: MJ
authors: Owen
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Nigel
authors: N
authors: Williams
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Michael C
authors: MC
authors: O'Donovan
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Anita
authors: A
authors: Thapar
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, UK.
authors: Peter
authors: P
authors: Holmans
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D015897:Comorbidity; D056915:DNA Copy Number Variations; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D006113:United Kingdom / Q000453:epidemiology
keywords: ADHD; ASD; CNVs; comorbidity; pathway analysis