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Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

Journal article
Authors O. O. Gudmundsson
G. B. Walters
A. Ingason
S. Johansson
T. Zayats
L. Athanasiu
I. E. Sonderby
O. Gustafsson
M. S. Nawaz
G. F. Jonsson
Lina Jonsson
P. M. Knappskog
E. Ingvarsdottir
K. Davidsdottir
S. Djurovic
G. P. S. Knudsen
R. B. Askeland
G. S. Haraldsdottir
G. Baldursson
P. Magnusson
E. Sigurdsson
D. F. Gudbjartsson
H. Stefansson
O. A. Andreassen
J. Haavik
T. Reichborn-Kjennerud
K. Stefansson
Published in Translational Psychiatry
Volume 9
ISSN 2158-3188
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Language en
Links dx.doi.org/10.1038/s41398-019-0599-...
Keywords deficit/hyperactivity disorder, psychiatric-disorders, 22q11.2 deletion, norwegian mother, cohort profile, child cohort, duplications, phenotype, genetics
Subject categories Psychiatry

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.

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