Skip to content

Research at St Andrews

Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3

Research output: Contribution to journalArticle

Author(s)

Nigel M. Williams, Barbara Franke, Eric Mick, Richard J. L. Anney, Christine M. Freitag, Michael Gill, Anita Thapar, Michael C. O'Donovan, Michael J. Owen, Peter Holmans, Lindsey Kent, Frank Middleton, Yanli Zhang-James, Lu Liu, Jobst Meyer, Thuy Trang Nguyen, Jasmin Romanos, Marcel Romanos, Christiane Seitz, Tobias J. Renner & 29 others Susanne Walitza, Andreas Warnke, Haukur Palmason, Jan Buitelaar, Nanda Rommelse, Alejandro Arias Vasquez, Ziarih Hawi, Kate Langley, Joseph Sergeant, Hans-Christoph Steinhausen, Herbert Roeyers, Joseph Biederman, Irina Zaharieva, Hakon Hakonarson, Josephine Elia, Anath C. Lionel, Jennifer Crosbie, Christian R. Marshall, Russell Schachar, Stephen W. Scherer, Alexandre Todorov, Susan L. Smalley, Sandra Loo, Stanley Nelson, Corina Shtir, Philip Asherson, Andreas Reif, Klaus-Peter Lesch, Stephen V. Faraone

School/Research organisations

Abstract

Objective: Attention 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.

Method: 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.

Results: 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.

Conclusions: 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.

Close

Details

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalAmerican Journal of Psychiatry
Volume169
Issue number2
DOIs
Publication statusPublished - Feb 2012

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. A case-control genome-wide association study of ADHD discovers a novel association with the tenascin R (TNR) gene

    Hawi, Z., Yates, H., Pinar, A., Johnson, B., Tong, J., Pugsley, K., Dark, C., Pauper, M., Klein, M., Heussler, H. S., Hiscock, H., Fornito, A., Tiego, J., Finlay, A., Vance, A., Gill, M., Kent, L. S. & Bellgrove, M. A., 18 Dec 2018, In : Translational Psychiatry. 8, 8 p., 284.

    Research output: Contribution to journalArticle

  2. Rare DNA variants in the brain derived neurotrophic factor gene increase risk for attention deficit hyperactivity disorder: a next generation sequencing study

    Hawi, Z., Cummins, T. D. R., Tong, J., Arcos-Burgos, M., Zhao, Q., Matthews, N., Newman, D. P., Johnson, B., Vance, A., Heussler, H. S., Levy, F., Easteal, S., Wray, N., Kenny, E., Morris, D., Kent, L., Gill, M. & Bellgrove, M., Apr 2017, In : Molecular Psychiatry. 22, 4, p. 580-584 5 p.

    Research output: Contribution to journalArticle

  3. GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder

    Deckert, J., Weber, H., Villmann, C., Lonsdorf, T. B., Richter, J., Andreatta, M., Arias-Vasquez, A., Hommers, L., Kent, L., Schartner, C., Cichon, S., Wolf, C., Schaefer, N., von Collenberg, C. R., Wachter, B., Blum, R., Schümann, D., Scharfenort, R., Schumacher, J., Forstner, A. J. & 27 others, Baumann, C., Schiele, M. A., Notzon, S., Zwanzger, P., Janzing, J. G. E., Galesloot, T., Kiemeney, L. A., Gajewska, A., Glotzbach-Schoon, E., Mühlberger, A., Alpers, G., Fydrich, T., Fehm, L., Gerlach, A. L., Kircher, T., Lang, T., Ströhle, A., Arolt, V., Wittchen, H-U., Kalisch, R., Büchel, C., Hamm, A., Nöthen, M. M., Romanos, M., Domschke, K., Pauli, P. & Reif, A., 2017, In : Molecular Psychiatry. 22, 2, p. 1431-1439 9 p.

    Research output: Contribution to journalArticle

  4. Pathway analysis in attention deficit hyperactivity disorder: an ensemble approach

    Mooney, M. A., McWeeney, S. K., Faraone, S. V., Hinney, A., Hebebrand, J., IMAGE2 Consortium, German ADHD GWAS Group, Nigg, J. T. & Wilmot, B., Sep 2016, In : American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics . 171, 6, p. 815-826

    Research output: Contribution to journalArticle

  5. Psychiatric gene discoveries shape evidence on ADHD's biology

    Thapar, A., Martin, J., Mick, E., Arias Vásquez, A., Langley, K., Scherer, S. W., Schachar, R., Crosbie, J., Williams, N., Franke, B., Elia, J., Glessner, J., Hakonarson, H., Owen, M. J., Faraone, S. V., O'Donovan, M. C., Holmans, P. & IMAGE 2 Consortium (incl Kent L), 2016, In : Molecular Psychiatry. 21, p. 1202-1207 6 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Gang membership, violence, and psychiatric morbidity

    Coid, JW., Ullrich, S., Keers, R., Bebbington, P., DeStavola, B., Kallis, C., Yang, M., Reiss, D., Jenkins, R. & Donnelly, P. D., 1 Sep 2013, In : American Journal of Psychiatry. 170, 9, p. 985-93

    Research output: Contribution to journalArticle

  2. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression

    Hamshere, M. L., Langley, K., Martin, J., Agha, S. S., Stergiakouli, E., Anney, R. J. L., Buitelaar, J., Faraone, S. V., Lesch, K-P., Neale, B. M., Franke, B., Sonuga-Barke, E., Asherson, P., Merwood, A., Kuntsi, J., Medland, S. E., Ripke, S., Steinhausen, H-C., Freitag, C., Reif, A. & 22 others, Renner, T. J., Romanos, M., Romanos, J., Warnke, A., Meyer, J., Palmason, H., Vasquez, A. A., Lambregts-Rommelse, N., Roeyers, H., Biederman, J., Doyle, A. E., Hakonarson, H., Rothenberger, A., Banaschewski, T., Oades, R. D., McGough, J. J., Kent, L., Williams, N., Owen, M. J., Holmans, P., O'Donovan, M. C. & Thapar, A., Aug 2013, In : American Journal of Psychiatry. 170, 8, p. 909-916 8 p.

    Research output: Contribution to journalArticle

  3. Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD

    Stergiakouli, E., Hamshere, M., Holmans, P., Langley, K., Zaharieva, I., Hawi, Z., Kent, L., Gill, M., Williams, N., Owen, M. J., O'Donovan, M., Thapar, A. & ADHD Subgrp, Psychiat GWAS Consortium, deCODE Genetics, Feb 2012, In : American Journal of Psychiatry. 169, 2, p. 186-194 9 p.

    Research output: Contribution to journalArticle

  4. Association of the KIAA0319 Dyslexia Susceptibility Gene With Reading Skills in the General Population

    Paracchini, S., Steer, C. D., Buckingham, L-L., Morris, A. P., Ring, S., Scerri, T., Stein, J., Pembrey, M. E., Ragoussis, J., Golding, J. & Monaco, A. P., Dec 2008, In : American Journal of Psychiatry. 165, 12, p. 1576-1584 9 p.

    Research output: Contribution to journalArticle

ID: 17585266

Top