title: Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures.
abstract: Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours.
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Lester
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Barclay
authors.forename: Simon N
authors.initials: SN
authors.lastname: Archer
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
authors.forename: Thalia C
authors.initials: TC
authors.lastname: Eley
authors.forename: Alice M
authors.initials: AM
authors.lastname: Gregory
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D011795:Surveys and Questionnaires; D013997:Time Factors; D006113:United Kingdom; D055815:Young Adult
chemical_list: D056930:ARNTL Transcription Factors; C486615:BMAL2 protein, human; C000595803:GNB3 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D020962:Heterotrimeric GTP-Binding Proteins
keywords: circadian expressed genes; genetic association; single nucleotide polymorphisms; sleep duration; sleep quality