title: Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder.
abstract: 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.
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hida
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Katayose
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kadotani
authors.affiliation: Department of Psychiatry, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.affiliation: Department of Psychiatry, Tokyo Metropolitan Police Hospital, Nakano, Tokyo 164-8541, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ebisawa
authors.affiliation: 1] Department of Somnology, Tokyo Medical University, Shinjuku, Tokyo 160-8402, Japan [2] Yoyogi Sleep Disorder Center, Shibuya, Tokyo 151-0053, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Japan Foundation for Neuroscience and Mental Health, Kodaira, Tokyo 187-8551, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Okawa
authors.affiliation: Japan Foundation for Neuroscience and Mental Health, Kodaira, Tokyo 187-8551, Japan.
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mishima
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000328:Adult; D000483:Alleles; D056926:CLOCK Proteins / Q000235:genetics*; D047389:Casein Kinase I / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D056931:Cryptochromes / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012890:Sleep / Q000502:physiology; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C538963:CRY1 protein, human; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; C539022:PER1 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; C509769:TIMELESS protein, human; D056926:CLOCK Proteins; C538943:CLOCK protein, human; D047389:Casein Kinase I