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The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes
Open accessAbstract
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
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“Brookes et al. (2006) in a genome-wide study provide speculative evidence that polymorphisms in PER 2 may be associated with ADHD in children, but the association was not significant at the study-wide or genome-wide level”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Brookes et al. (2006)
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“it has been proposed that valid endophenotypes can be found at a higher rate in unaffected family members than in the general population 23,24.”
From Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings (2015) · cites this paper as [24]
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Self-citation
Metadata
- Authors
- Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., Aneey, R., Franke, B., Gill, M., Ebstein, R., Buitelaar, J., Sham, P., Campbell, D., Knight, J., Andreou, P., Altink, M., Arnold, R., Boer, F., Buschgens, C., Butler, L., Christiansen, H., Feldman, L., Fleischman, K., Fliers, E., Howe-Forbes, R., Goldfarb, A., Heise, A., Gabriëls, I., Korn-Lubetzki, I., Marco, R., Medad, S., Minderaa, R., Mulas, F., Müller, U., Mulligan, A., Rabin, K., Rommelse, N., Sethna, V, Sorohan, J., Uebel, H., Psychogiou, L., Weeks, A., Barrett, R., Craig, I., Banaschewski, T., Sonuga-Barke, E., Eisenberg, J., Kuntsi, J., Manor, I., McGuffin, P., Miranda, A., Oades, R. D., Plomin, R., Roeyers, H., Rothenberger, A., Sergeant, J., Steinhausen, H.-C., Taylor, E., Thompson, M., Faraone, S. V., Asherson, P., & Johansson, L.
- Affiliations
- St. James's Hospital (IE)
- Radboud University Nijmegen (NL)
- Herzog Hospital (IL)
- Geha Mental Health Center (IL)
- University of Göttingen (DE)
- Ghent University (BE)
- Shaare Zedek Medical Center (IL)
- Universitat de València (ES)
- University Medical Center Groningen (NL)
- University of Zurich (CH)
- Vrije Universiteit Amsterdam (NL)
- University of Southampton (GB)
- SUNY Upstate Medical University (US)
- Corresponding author
- Asherson, P
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2006-08-08
- Volume
- 11
- Issue
- 10
- Pages
- 934-953
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2149164700
- Cited by
- 533
- References
- 92
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 13 · 2019: 13 · 2018: 14 · 2017: 19 · 2016: 35 · 2015: 27 · 2014: 34 · 2013: 26 · 2012: 38
- FWCI
- 36.39
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-11-28)
- Open access
- bronze
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DuEPublico (University of Duisburg-Essen) (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- GRO (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH062873)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, combined type ADHD, candidate gene association, single nucleotide polymorphisms, DRD4, DAT1, dopaminergic pathways, serotonin pathway, circadian rhythm genes, tryptophan hydroxylase 2, monoamine oxidase A, phenylethanolamine N-methyltransferase, Hes1, ADRB2, synaptophysin, β-arrestin2
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Genetic Markers, Haplotypes, Humans, Monoamine Oxidase, Pedigree, Receptors, Nicotinic, Tryptophan Hydroxylase, Oncogene Proteins, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Siblings, Dopamine Plasma Membrane Transport Proteins, Receptors, Dopamine D4, Synaptosomal-Associated Protein 25
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