title: Association of CLOCK, ARNTL, PER2, and GNB3 polymorphisms with diurnal preference in a Korean population.
abstract: Polymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i.e. "morningness," "activity planning," and "morning alertness," were extracted from the CSM. No significant associations were observed between CSM scores and CLOCK (rs1801260) genotype or T allele carrier status, CSM scores and ARNTL (rs2278749) C allele carrier status, and CSM scores and GNB3 (rs5443) genotype or C allele carrier status. However, total CSM scores and scores of its subscales were significantly associated with PER2 (rs934945) genotype (p = 0.010, p = 0.018, and p = 0.005 for total, morningness, and activity planning, respectively) and G allele carrier status (p = 0.003, p = 0.005, and p = 0.002 for total, morningness, and activity planning, respectively). The best model result obtained by performing multifactor dimensionality reduction analysis ([Formula: see text]2= 11.2798, p = 0.0008) indicated that interaction among C/T single nucleotide polymorphism (SNP) in ARNTL, C/T SNP in GNB3, and G/A SNP in PER2 synergistically affected the risk associated with diurnal preference toward eveningness. These results suggest that circadian gene PER2 is associated with diurnal preference in healthy Korean population. Although polymorphisms in ARNTL and GNB3 were not significantly associated with diurnal preference, their interactions with the polymorphism in PER2 may synergistically increase the risk of diurnal preference toward eveningness.
authors.affiliation: a Department of Biomedical Science , Korea University College of Medicine.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: b Department of Psychiatry , Korea University College of Medicine.|c Sleep-Wake Disorders Center, Anam Hospital, Korea University , Seoul.
authors.forename: Chul-Hyun
authors.initials: CH
authors.lastname: Cho
authors.affiliation: a Department of Biomedical Science , Korea University College of Medicine.|b Department of Psychiatry , Korea University College of Medicine.|c Sleep-Wake Disorders Center, Anam Hospital, Korea University , Seoul.
authors.forename: Heon-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: a Department of Biomedical Science , Korea University College of Medicine.
authors.forename: Joung Ho
authors.initials: JH
authors.lastname: Moon
authors.affiliation: d Department of Psychiatry , Gachon University School of Medicine , Incheon.
authors.forename: Seung-Gul
authors.initials: SG
authors.lastname: Kang
authors.affiliation: b Department of Psychiatry , Korea University College of Medicine.|c Sleep-Wake Disorders Center, Anam Hospital, Korea University , Seoul.
authors.forename: Ho-Kyoung
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: e Department of Psychiatry , Inje University College of Medicine , Ilsan , Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: b Department of Psychiatry , Korea University College of Medicine.|c Sleep-Wake Disorders Center, Anam Hospital, Korea University , Seoul.
authors.forename: Leen
authors.initials: L
authors.lastname: Kim
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D044466:Asian People; D056926:CLOCK Proteins / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; C000595803:GNB3 protein, human; D005819:Genetic Markers; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; D020962:Heterotrimeric GTP-Binding Proteins
keywords: ARNTL; CLOCK; Diurnal preference; GNB3; PER2; polymorphism