An international multicenter association study of the serotonin transporter gene in persistent ADHD
Open accessAbstract
Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR ) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded.
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From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Landaas et al., 2010
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Attention-Deficit Hyperactivity Disorder: Genetic, Pharmacogenetic, and Metabolomic Insights
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- Authors
- Landaas, E. T., Johansson, S., Jacobsen, K. K., Ribasés, M., Bosch, R., Sánchez‐Mora, C., Jacob, C. P., Boreatti‐Hümmer, A., Kreiker, S., Lesch, K. ‐., Kiemeney, L. A., Kooij, J. J. S., Kan, C., Buitelaar, J. K., Faraone, S. V., Halmøy, A., Ramos‐Quiroga, J. A., Cormand, B., Reif, A., Franke, B., Mick, E., Knappskog, P. M., & Haavik, J.
- Affiliations
- Haukeland University Hospital (NO)
- Vall d'Hebron Hospital Universitari (ES)
- University of Würzburg (DE)
- Radboud University Medical Center (NL)
- PsyQ (NL)
- Radboud University Nijmegen (NL)
- SUNY Upstate Medical University (US)
- University of Bergen (NO)
- Universitat Autònoma de Barcelona (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Harvard University (US)
- Corresponding author
- Haavik, J.
- ORCID
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2010-07
- Volume
- 9
- Issue
- 5
- Pages
- 449-458
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2099749295
- Cited by
- 55
- References
- 61
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 10 · 2014: 7 · 2013: 4 · 2012: 5
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 581, TRR‐58, RE1632/1-1, SFB TRR 58)
- Bundesministerium für Bildung und Forschung
- Fonds Psychische Gezondheid
- Helse Vest
- Norges Forskningsråd
- Hersenstichting
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- 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, adult ADHD, serotonin transporter gene, serotonin transporter, 5-HTTLPR, promoter polymorphism, single nucleotide polymorphisms, genetic association, sex differences, meta-analysis, rare variants, serotonergic neurotransmission
- MeSH terms
- Adolescent, Adult, Age Factors, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Depressive Disorder, Female, Germany, Humans, Male, Netherlands, Norway, Reference Values, Sex Factors, Spain, United States, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Serotonin Plasma Membrane Transport Proteins, Young Adult, Genetic Association Studies
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