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Biological overlap of attention-deficit/hyperactivity disorder and autism spectrum disorder: evidence from copy number variants

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Author(s)

Joanna Martin, Miriam Cooper, Marian L. Hamshere, Andrew Pocklington, Stephen W. Scherer, Lindsey Kent, Michael Gill, Michael J. Owen, Nigel Williams, Michael C. O'Donovan, Anita Thapar, Peter Holmans

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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. Method: 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. Conclusion: 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.

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Original languageEnglish
Pages (from-to)761-770
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume53
Issue number7
Early online date21 Apr 2014
DOIs
Publication statusPublished - Jul 2014

    Research areas

  • ADHD, ASD, Pathway analysis, CNVs, Comorbidity

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ID: 140339784