Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder

Sci Rep. 2014 Sep 9;4:6309. doi: 10.1038/srep06309.


A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Adult
  • Alleles
  • CLOCK Proteins / genetics*
  • Casein Kinase I / genetics
  • Cell Cycle Proteins / genetics
  • Circadian Clocks / genetics*
  • Circadian Clocks / physiology
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • Cryptochromes / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Period Circadian Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Sleep / physiology
  • Sleep Disorders, Circadian Rhythm / genetics*


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • CRY1 protein, human
  • Cell Cycle Proteins
  • Cryptochromes
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • PER1 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • TIMELESS protein, human
  • CLOCK Proteins
  • CLOCK protein, human
  • Casein Kinase I