Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticle

Author(s)

Evangelia Stergiakouli, Marian Hamshere, Peter Holmans, Kate Langley, Irina Zaharieva, Ziarah Hawi, Lindsey Kent, Michael Gill, Nigel Williams, Michael J. Owen, Michael O'Donovan, Anita Thapar, ADHD Subgrp, Psychiat GWAS Consortium, deCODE Genetics

School/Research organisations

Abstract

Objective: A major motivation for seeking disease-associated genetic variation is to identify novel risk processes. Although rare copy number variants (CNVs) appear to contribute to attention deficit hyperactivity disorder (ADHD), common risk variants (single-nucleotide polymorphisms [SNPs]) have not yet been detected using genome-wide association studies (GWAS). This raises the concern as to whether future larger-scale, adequately powered GWAS will be worthwhile. The authors undertook a GWAS of ADHD and examined whether associated SNPs, including those below conventional levels of significance, influenced the same biological pathways affected by CNVs.

Method: The authors analyzed genomewide SNP frequencies in 727 children with ADHD and 5,081 comparison subjects. The gene sets that were enriched in a pathway analysis of the GWAS data (the top 5% of SNPs) were tested for an excess of genes spanned by large, rare CNVs in the children with ADHD.

Results: No SNP achieved genome-wide significance levels. As previously reported in a subsample of the present study, large, rare CNVs were significantly more common in case subjects than comparison subjects. Thirteen biological pathways enriched for SNP association significantly overlapped with those enriched for rare CNVs. These included cholesterol-related and CNS development pathways. At the level of individual genes, CHRNA7, which encodes a nicotinic receptor subunit previously implicated in neuropsychiatric disorders, was affected by six large duplications in case subjects (none in comparison subjects), and SNPs in the gene had a gene-wide p value of 0.0002 for association in the GWAS.

Conclusions: Both common and rare genetic variants appear to be relevant to ADHD and index-shared biological pathways.

Close

Details

Original languageEnglish
Pages (from-to)186-194
Number of pages9
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., Vance, A., Hiscock, H., Fornito, A., Tiego, J., Finlay, A., Franke, B., 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. Advance online, 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 othersBaumann, 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, 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 othersRenner, 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. Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3

    Williams, N. M., Franke, B., Mick, E., Anney, R. J. L., Freitag, C. M., Gill, M., Thapar, A., O'Donovan, M. C., Owen, M. J., Holmans, P., Kent, L., Middleton, F., Zhang-James, Y., Liu, L., Meyer, J., Trang Nguyen, T., Romanos, J., Romanos, M., Seitz, C., Renner, T. J. & 29 othersWalitza, S., Warnke, A., Palmason, H., Buitelaar, J., Rommelse, N., Vasquez, A. A., Hawi, Z., Langley, K., Sergeant, J., Steinhausen, H-C., Roeyers, H., Biederman, J., Zaharieva, I., Hakonarson, H., Elia, J., Lionel, A. C., Crosbie, J., Marshall, C. R., Schachar, R., Scherer, S. W., Todorov, A., Smalley, S. L., Loo, S., Nelson, S., Shtir, C., Asherson, P., Reif, A., Lesch, K-P. & Faraone, S. V., Feb 2012, In : American Journal of Psychiatry. 169, 2, p. 195-204 10 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: 17585023