ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Ramos-Quiroga, J. A.,201424269040
Citation	Ramos-Quiroga JA, Sanchez-Mora C, Casas M, Garcia-Martinez I, Bosch R, Nogueira M, Corrales M, Palomar G, Vidal R, Coll-Tane M, Bayes M, Cormand B, Ribases M (2014) Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder. J Psychiatr Res 49: 60-7. doi: 10.1016/j.jpsychires.2013.10.022
Study Design	case-control
Study Type	Genome-wide CNV analysis
Sample Size	400 adults with ADHD and 526 screened controls.
Predominant Ethnicity	Caucasian
Population	Spainish
Gender	Sixty-seven percent of patients were male (n = 267).
Age Group	Adults : The average age at assessment was 31.16 years (SD = 12.5) for patients and 33.2 years (SD = 21.5) for controls.

Detail Info

Summary	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.
Total Sample	A total sample of 400 ADHD subjects (254 combined, 133 inattentive,9 hyperactive-impulsive and four with undefined subtype) and 526 sex-matched unrelated controls were recruited from hospital Vall d¡¯Hebron, Barcelona (Spain).
Sample Collection	A total sample of 400 ADHD subjects (254 combined, 133 inattentive, 9 hyperactive-impulsive and four with undefined subtype) and 526 sex-matched unrelated controls were recruited from Hospital Vall d¡¯Hebron, Barcelona (Spain).
Diagnosis Description	The ADHD diagnosis was based on the Structured Clinical Interview for DSM-IV Axis I and Axis II Disorders (SCID-I and SCIDII) and the Conners¡¯ Adult ADHD Diagnostic Interview for DSM-IV (CAADID). The level of impairment was measured by the Clinical Global Impression (CGI) included in the CAADID Part II and the Sheehan Disability Inventory. Exclusion criteria for the adult and childhood Spanish patients cohorts were IQ < 70; pervasive developmental disorders; schizophrenia or other psychotic disorders; the presence of mood, anxiety or personality disorders that might explain ADHD symptoms; adoption; sexual or physical abuse; birth weight <1.5 kg; and other neurological or systemic disorders that might explain ADHD symptoms. All controls consisted of Caucasian blood donors in which DSMIV life-time ADHD symptomatology was excluded under the following criteria: (1) not having previously been diagnosed with ADHD and (2) answering negatively to the life-time presence of the following DSM-IV ADHD symptoms: (a) often has trouble keeping attention on tasks, (b) often loses things needed for tasks, (c) often fidgets with hands or feet or squirms in seat and (d) often gets up from seat when remaining in seat is expected. Due to ethics concerns, all subjects included as controls were adults.
Technique	Genome-wide genotyping was performed with the Illumina HumanOmni1-Quad platform.
Analysis Method	Significance of the burden comparisons was assessed through permutation one-sided tests (100,000 permutations) using PLINK (version 1.06).
Result Description	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.

CNVs reported by this study (count: 4)

Name	Symbol in Literature	Type	Inheritance	Author Comments
CNV_Ramos[2014]_4	chr19: 1,083,637-1,222,274	Duplication		Rare CNVs were identified in more than one ADHD patient. Rare CNVs were identified in more than one ADHD patient.
CNV_Ramos[2014]_3	chr10: 63,694,654-63,798,960	Duplication		Rare CNVs were identified in more than one ADHD patient. Rare CNVs were identified in more than one ADHD patient.
CNV_Ramos[2014]_2	chr8: 16,041,550-16,763,189	Deletion		Rare CNVs were identified in more than one ADHD patient. Rare CNVs were identified in more than one ADHD patient.
CNV_Ramos[2014]_1	chr6: 33,071,762-33,229,165	Deletion		Rare CNVs were identified in more than one ADHD patient. Rare CNVs were identified in more than one ADHD patient.