Human CLOCK gene-associated attention deficit hyperactivity disorder-related features in healthy adults: quantitative association study using Wender Utah Rating Scale
Abstract
Circadian rhythm disturbance is highly prevalent in attention deficit hyperactivity disorder (ADHD). Recently, the association between the CLOCK gene and ADHD has been demonstrated in clinical samples, and the CLOCK gene's role was thought to be mediated by rhythm dysregulation. Meanwhile, ADHD has been suggested as the extreme end of a continuously distributed trait that can be found in the general population. Therefore, we examined two possibilities: (1) an ADHD-related continuous trait may be associated with the CLOCK gene, and (2) this association may be mediated by the degree of individuals' evening preference. To explore these possibilities, we performed a quantitative trait locus association study with a sample of 1,289 healthy adults. The Wender Utah Rating Scale (WURS) and the Composite Scale of Morningness (CSM) were utilized to measure the quantitative traits. Quantitative association analysis was performed using PLINK software. We found that rs1801260 (=T3111C) was associated with WURS scores in both allele-wise (p = 0.018) and haplotype-wise analyses (range of p values: 0.0155-0.0171) in male participants only. After controlling for the CSM total score as a covariate, the strength of the association did not change at all, suggesting that the association was not mediated by evening preference. Despite the very weak association signal, our results provide evidence that the CLOCK gene's association with ADHD in clinical samples may be generalizable to traits measured in the normal population. However, as our results failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits.
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The T3111C SNP in CLOCK is associated with ADHD symptoms in males.
“Jeong et al. (2014) report that the T3111C SNP in CLOCK is also associated with ADHD symptoms in males.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Jeong et al. (2014)
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Coogan, A. N., & McGowan, N. M. (2017) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-016-0214-5 · Cited by 208 · see citing works
- Authors
- Jeong, S. H., Yu, J.-C., Lee, C. H., Choi, K.-S., Choi, J.-E., Kim, S. H., & Joo, E.-J.
- Affiliations
- Eulji University (KR)
- Seoul National University (KR)
- Corresponding author
- Joo, Eun-Jeong
- Venue
- European Archives of Psychiatry and Clinical Neuroscience
- Published
- 2013-09-26
- Volume
- 264
- Issue
- 1
- Pages
- 71-81
- ISSN
- 0003-9373 (ISSN-L)
- 0940-1334
- 1433-8491
- OpenAlex
- W2079497439
- Cited by
- 28
- References
- 62
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Archives of Psychiatry and Clinical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- 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
- attention deficit hyperactivity disorder, clock genes, circadian rhythm, quantitative trait loci, Wender Utah Rating Scale, Composite Scale of Morningness, genetic association
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Circadian Rhythm, Female, Genotype, Humans, Male, Psychiatric Status Rating Scales, Statistics as Topic, Young Adult, Genetic Association Studies, CLOCK Proteins
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