The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample

Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):101-4. doi: 10.1002/ajmg.b.30110.


Sleep timing is influenced by the circadian system. Morningness-eveningness (ME) preference in humans is affected by the free-running period, which is determined by circadian clock-relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3'-flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne-Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 +/- 1.4 (range, 25-73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • CLOCK Proteins
  • Circadian Rhythm / physiology*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Japan
  • Male
  • Polymorphism, Single Nucleotide*
  • Sleep / genetics*
  • Sleep / physiology
  • Time Factors
  • Trans-Activators / genetics*


  • Trans-Activators
  • CLOCK Proteins
  • CLOCK protein, human