Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder
Open accessAbstract
Objective Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power.Method We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis.Results No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder.Conclusions Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability.
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The role of the dopamine, noradrenaline, serotonin and neurite outgrowth systems is supported by GWAS-based gene-set analyses reporting that, as a group, genes regulating these systems were associated with ADHD and hyperactivity or impulsivity.
“Nevertheless, the role of the dopamine, noradrenaline, serotonin and neurite outgrowth systems is supported by genome-wide association studybased gene-set analyses reporting that, as a group, genes regulating these systems were associated with ADHD and hyperactivity or impulsivity 46,49,50 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [46]
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Attention Deficit Hyperactivity Disorder
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Self-citation
- Authors
- Neale, B. M., Medland, S. E., Ripke, S., Asherson, P., Franke, B., Lesch, K.-P., Faraone, S. V., Nguyen, T. T., Schäfer, H., Holmans, P., Daly, M., Steinhausen, H.-C., Freitag, C., Reif, A., Renner, T. J., Romanos, M., Romanos, J., Walitza, S., Warnke, A., Meyer, J., Palmason, H., Buitelaar, J., Vasquez, A. A., Lambregts-Rommelse, N., Gill, M., Anney, R. J. L., Langely, K., O'Donovan, M., Williams, N., Owen, M., Thapar, A., Kent, L., Sergeant, J., Roeyers, H., Mick, E., Biederman, J., Doyle, A., Smalley, S., Loo, S., Hakonarson, H., Elia, J., Todorov, A., Miranda, A., Mulas, F., Ebstein, R. P., Rothenberger, A., Banaschewski, T., Oades, R. D., Sonuga-Barke, E., McGough, J., Nisenbaum, L., Middleton, F., Hu, X., & Nelson, S.
- Affiliations
- Broad Institute (US)
- King's College London (GB)
- Radboud University Medical Center (NL)
- University of Würzburg (DE)
- SUNY Upstate Medical University (US)
- Philipps University of Marburg (DE)
- Medical Research Council (GB)
- University of Basel (CH)
- Goethe University Frankfurt (DE)
- University of Zurich (CH)
- Universität Trier (DE)
- St. James's Hospital (IE)
- Cardiff University (GB)
- University of St Andrews (GB)
- Vrije Universiteit Amsterdam (NL)
- Ghent University (BE)
- Harvard University (US)
- University of California, Los Angeles (US)
- Children's Hospital of Philadelphia (US)
- Washington University in St. Louis (US)
- Universitat de València (ES)
- Hospital Universitari i Politècnic La Fe (ES)
- Hebrew University of Jerusalem (IL)
- University of Göttingen (DE)
- University of Duisburg-Essen (DE)
- Eli Lilly (United States) (US)
- Pfizer (United States) (US)
- Corresponding author
- Faraone, Stephen V.
- ORCID
- Neale, Benjamin M.
- Medland, Sarah E.
- Ripke, Stephan
- Asherson, Philip
- Franke, Barbara
- Lesch, Klaus-Peter
- Faraone, Stephen V.
- Nguyen, Thuy Trang
- Holmans, Peter
- Daly, Mark
- Freitag, Christine
- Reif, Andreas
- Romanos, Marcel
- Walitza, Susanne
- Buitelaar, Jan
- Gill, Michael
- Anney, Richard J.L.
- Williams, Nigel
- Owen, Michael
- Thapar, Anita
- Kent, Lindsey
- Sergeant, Joseph
- Roeyers, Herbert
- Mick, Eric
- Biederman, Joseph
- Doyle, Alysa
- Smalley, Susan
- Loo, Sandra
- Hakonarson, Hakon
- Elia, Josephine
- Miranda, Ana
- Ebstein, Richard P.
- Rothenberger, Aribert
- Banaschewski, Tobias
- Sonuga-Barke, Edmund
- McGough, James
- Middleton, Frank
- Hu, Xiaolan
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 49
- Issue
- 9
- Pages
- 884-897
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC2928252
- OpenAlex
- W2168505085
- Cited by
- 450
- References
- 40
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 11 · 2022: 13 · 2021: 14 · 2020: 23 · 2019: 25 · 2018: 45 · 2017: 62 · 2016: 50 · 2015: 40 · 2014: 53 · 2013: 33 · 2012: 27
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- DuEPublico (University of Duisburg-Essen) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- GRO (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Wellcome Trust
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (480- 05-003)
- National Institutes of Health (5k23mh066275-05)
- National Institute of Mental Health (R01MH058277, R01 MH 62873, U01MH085518, R01MH083823, R01MH081803, R01MH58277, R01MH062873, K23MH066275, K23MH066275-01, R13MH059126, U01MH085515, R01MH080403)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, genetic risk variants, heritability, candidate genes, rare variants, single nucleotide polymorphisms, trios
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Female, Humans, Male, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Association Studies
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