CLOCK Gene Variants Associate with Sleep Duration in Two Independent Populations

Karla V. Allebrandt, Maris Teder-Laving, Mahmut Akyol, Irene Pichler, Bertram Mueller-Myhsok, Peter Pramstaller, Martha Merrow, Thomas Meitinger, Andreas Metspalu, Till Roenneberg*, Bertram Müller-Myhsok

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Sleep is an active and complex behavior, yet it has two straightforward properties-timing and duration. Clock genes are associated with dysfunctional timing of sleep, mood, and obesity disorders, which are commonly associated with sleep duration.

Methods: Sleep duration was assessed in Central Europe, Estonia, and South Tyrol (n approximate to 77,000) with the Munich ChronoType Questionnaire. It showed a Gaussian distribution in all investigated populations after averaging over a standard workweek and normalization according to age and gender. A follow-up, two-stage design, linkage disequilibrium-based association study was conducted with subjects from South Tyrol (discovery sample; n = 283) and with short (<7 hours) and long (> 8.5 hours) sleepers from Estonia (confirmation sample; n = 1011). One hundred ninety-four single nucleotide polymorphism markers covering 19 candidate clock genes were genotyped in the discovery sample, and two of the best association signals (analyzed by a linear regression model) were investigated in the confirmation sample.

Results: Single and multi-marker associations were found within a CLOCK gene intronic region (rs12649507 and rs11932595). In a meta-analysis between South Tyrol and Estonia association signals, rs12649507 (p = .0087) remained significant. Significance persisted only for the multiple-marker association signal of the rs12649507/rs11932595 haplotype GGAA with long sleep (p = .0015).

Conclusions: We report an association between variants of the human CLOCK gene and sleep duration in two independent populations. This adds another putative function for CLOCK besides its possible involvement in circadian timing, depression, obesity, and personality.

Original languageEnglish
Pages (from-to)1040-1047
Number of pages8
JournalBiological Psychiatry
Volume67
Issue number11
DOIs
Publication statusPublished - 1-Jun-2010

Keywords

  • CLOCK
  • sleep duration
  • clock genes
  • MCTQ
  • short sleepers
  • long sleepers
  • CIRCADIAN CLOCK
  • TRANSCRIPTION FACTOR
  • BIPOLAR DISORDER
  • POLYMORPHISM
  • TIME
  • PREFERENCE
  • MOUSE
  • SUSCEPTIBILITY
  • PERSPECTIVES
  • ADOLESCENTS

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