Human CLOCK gene-associated attention deficit hyperactivity disorder-related features in healthy adults: quantitative association study using Wender Utah Rating Scale

  • Seong Hoon Jeong
  • Je-Chun Yu
  • Chang Hwa Lee
  • Kyeong-Sook Choi
  • Jung-Eun Choi
  • Se Hyun Kim
  • Eun-Jeong JooEmail author
Original Paper


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.


Association study Attention deficit hyperactivity disorder CLOCK gene Circadian rhythm Composite Scale of Morningness Wender Utah Rating Scale 



This work was supported by National Research Foundation of Korea Grant funded by the Korean Government (2011-0003164). The English in this document has been checked by at least two professional editors, both native speakers of English. For a certificate, please see: (

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Seong Hoon Jeong
    • 1
  • Je-Chun Yu
    • 1
  • Chang Hwa Lee
    • 1
  • Kyeong-Sook Choi
    • 1
  • Jung-Eun Choi
    • 2
  • Se Hyun Kim
    • 3
  • Eun-Jeong Joo
    • 4
    Email author
  1. 1.Department of PsychiatryEulji University School of MedicineDaejeonKorea
  2. 2.Department of PsychiatrySeoul Metropolitan EunPyeong HospitalSeoulKorea
  3. 3.Institute of Human Behavioral Medicine, Medical Research InstituteSeoul National UniversitySeoulKorea
  4. 4.Department of PsychiatryEulji University School of MedicineNowon-GuSouth Korea

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