title: Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder.
abstract: Attention-deficit and hyperactivity disorder (ADHD) is a common psychiatric disorder with a worldwide prevalence of 5-6% in children and 4.4% in adults. Recently, copy number variations (CNVs) have been implicated in different neurodevelopmental disorders such as ADHD. Based on these previous reports that focused on pediatric cohorts, we hypothesize that structural variants may also contribute to adult ADHD and that such genomic variation may be enriched for CNVs previously identified in children with ADHD. To address this issue, we performed for the first time a whole-genome CNV study on 400 adults with ADHD and 526 screened controls. In agreement with recent reports in children with ADHD or in other psychiatric disorders, we identified a significant excess of insertions in ADHD patients compared to controls. The overall rate of CNVs >100 kb was 1.33 times higher in ADHD subjects than in controls (p = 2.4e-03), an observation mainly driven by a higher proportion of small events (from 100 kb to 500 kb; 1.35-fold; p = 1.3e-03). These differences remained significant when we considered CNVs that overlap genes or when structural variants spanning candidate genes for psychiatric disorders were evaluated, with duplications showing the greatest difference (1.41-fold, p = 0.024 and 2.85-fold, p = 8.5e-03, respectively). However, no significant enrichment was detected in our ADHD cohort for childhood ADHD-associated CNVs, CNVs previously identified in at least one ADHD patient or CNVs previously implicated in autism or schizophrenia. In conclusion, our study provides tentative evidence for a higher rate of CNVs in adults with ADHD compared to controls and contributes to the growing list of structural variants potentially involved in the etiology of the disease.
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain; Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Josep-Antoni
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain; Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Mora
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain; Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Casas
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Garcia-Martínez
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosch
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Nogueira
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Montse
authors.initials: M
authors.lastname: Corrales
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Palomar
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Vidal
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Coll-Tané
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Bayés
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.affiliation: Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain; Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. Electronic address: marta.ribases@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Ribasés
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002869:Chromosome Aberrations; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
keywords: Attention-deficit and hyperactivity disorder (ADHD); Autism; Copy number variation (CNV); Schizophrenia