Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsWilliams, Nigel M
Anney, Richard J L
Freitag, Christine M
O'Donovan, Michael C
Owen, Michael J
Nguyen, Thuy Trang
Renner, Tobias J
Vasquez, Alejandro Arias
Lionel, Anath C
Marshall, Christian R
Scherer, Stephen W
Smalley, Susan L
Faraone, Stephen V
MetadataShow full item record
CitationAm J Psychiatry 2012, 169(2):195-204
AbstractAttention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium. The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.
DescriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.
RightsArchived with thanks to The American journal of psychiatry
- Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD.
- Authors: Stergiakouli E, Hamshere M, Holmans P, Langley K, Zaharieva I, deCODE Genetics., Psychiatric GWAS Consortium., Hawi Z, Kent L, Gill M, Williams N, Owen MJ, O'Donovan M, Thapar A
- Issue date: 2012 Feb
- Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis.
- Authors: Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K, Fossdal R, Stefansson H, Stefansson K, Magnusson P, Gudmundsson OO, Gustafsson O, Holmans P, Owen MJ, O'Donovan M, Thapar A
- Issue date: 2010 Oct 23
- Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder.
- Authors: Jarick I, Volckmar AL, Pütter C, Pechlivanis S, Nguyen TT, Dauvermann MR, Beck S, Albayrak Ö, Scherag S, Gilsbach S, Cichon S, Hoffmann P, Degenhardt F, Nöthen MM, Schreiber S, Wichmann HE, Jöckel KH, Heinrich J, Tiesler CM, Faraone SV, Walitza S, Sinzig J, Freitag C, Meyer J, Herpertz-Dahlmann B, Lehmkuhl G, Renner TJ, Warnke A, Romanos M, Lesch KP, Reif A, Schimmelmann BG, Hebebrand J, Scherag A, Hinney A
- Issue date: 2014 Jan
- Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder.
- Authors: Ramos-Quiroga JA, Sánchez-Mora C, Casas M, Garcia-Martínez I, Bosch R, Nogueira M, Corrales M, Palomar G, Vidal R, Coll-Tané M, Bayés M, Cormand B, Ribasés M
- Issue date: 2014 Feb
- Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree.
- Authors: Lesch KP, Selch S, Renner TJ, Jacob C, Nguyen TT, Hahn T, Romanos M, Walitza S, Shoichet S, Dempfle A, Heine M, Boreatti-Hümmer A, Romanos J, Gross-Lesch S, Zerlaut H, Wultsch T, Heinzel S, Fassnacht M, Fallgatter A, Allolio B, Schäfer H, Warnke A, Reif A, Ropers HH, Ullmann R
- Issue date: 2011 May