CLOCK gene variants associate with sleep duration in two independent populations.
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 approximately 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.
Centre for Chronobiology, Ludwig Maximilians University of Munich, Munich, Germany.
Karla V
KV
Allebrandt
Maris
M
Teder-Laving
Mahmut
M
Akyol
Irene
I
Pichler
Bertram
B
Müller-Myhsok
Peter
P
Pramstaller
Martha
M
Merrow
Thomas
T
Meitinger
Andreas
A
Metspalu
Till
T
Roenneberg
D000483:Alleles; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004957:Estonia; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D010641:Phenotype; D012737:Sex Factors; D012890:Sleep / Q000235:genetics*; D013997:Time Factors
D056926:CLOCK Proteins; C538943:CLOCK protein, human