A polymorphism at the 3′‐untranslated region of the CLOCK gene is associated with adult attention‐deficit hyperactivity disorder
Abstract
Attention‐deficit hyperactivity disorder (ADHD) is frequently found in childhood and persists in about 50% of cases into adulthood. Several studies demonstrate a relationship between ADHD, circadian rhythmicity and sleeping disturbances in unmedicated ADHD patients. Since ADHD is a very complex disease with a high genetic load involving multiple genes of moderate effect, we hypothesized a link between adult ADHD and genes involved in the circadian timekeeping system. A 3′‐UTR polymorphism of the circadian locomotor output cycles protein kaput (CLOCK) gene, rs1801260, has been linked to disturbed sleep patterns, although both the C‐allele and more controversially the T‐allele have been proposed as risk factors for different measures of evening preference. This study compared self‐rating and interview based measures of ADHD psychopathology of 143 subjects with and without ADHD with their rs1801260 genotype to test the hypothesis that ADHD is linked to one of the alleles of the CLOCK polymorphism. The T > C single nucleotide polymorphism rs1801260 was genotyped in DNA isolated from blood samples. The associations between genotype and ADHD‐scores were compared using non‐parametric ANCOVA with post hoc pairwise comparisons. There was a strong, significant association (P < 0.001) between each of the adult ADHD assessments and the rs1801260 polymorphism with at least one T‐mutation being the risk allele. This is the first study suggesting that a polymorphism of a gene within the circadian “clock” mechanism is a direct or linked contributing factor in adult ADHD. © 2007 Wiley‐Liss, Inc.
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The T3111C SNP in CLOCK is associated with ADHD symptoms in a forensic, adult male population of 143, with the T allele conferring risk.
“Kissling et al. (2008) reported that the T3111C single-nucleotide polymorphism (SNP) in CLOCK is associated with ADHD symptoms in a forensic, adult male population of 143, with the T allele conferring risk.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Kissling et al. (2008)
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- Authors
- Kissling, C., Retz, W., Wiemann, S., Coogan, A. N., Clement, R. M., Hünnerkopf, R., Conner, A. C., Freitag, C. M., Rösler, M., & Thome, J.
- Affiliations
- Swansea University (GB)
- Saarland University (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Thome, Johannes
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2007-10-18
- Volume
- 147B
- Issue
- 3
- Pages
- 333-338
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2124871602
- Cited by
- 109
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 10
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Maynooth University ePrints and eTheses Archive (Maynooth University) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- adult ADHD, clock genes, 3' untranslated region polymorphism, circadian rhythm, genetic susceptibility, sleep disorders, single nucleotide polymorphisms
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Base Sequence, Genotype, Humans, Male, Polymorphism, Genetic, Trans-Activators, DNA Primers, 3' Untranslated Regions, CLOCK Proteins
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