title: Association between CLOCK 3111T/C and preferred circadian phase in Korean patients with bipolar disorder.
abstract: Genes associated with circadian rhythms have been suggested to play an important role in the pathophysiology of bipolar disorder. A single nucleotide polymorphism (SNP) in the 3'-flanking region of CLOCK (3111T/C; rs1801260) has been reported to be associated with sleep disturbances and an increased recurrence rate in patients with bipolar disorder. We examined the association of CLOCK 3111T/C with bipolar disorder in 260 patients and 350 controls in a Korean population. CLOCK 3111T/C showed significant allelic and genotypic associations with bipolar disorder (P=0.012, P=0.033, respectively). Morningness/eveningness (M/E) was evaluated using the Composite Scale of Morningness (CSM) in 108 patients with bipolar disorder. In the subgroup analysis of the highest and lowest 25th percentile of M/E scores, significantly more C allele carriers were found among extreme evening types than among extreme morning types (P=0.041). After correcting for age, C allele carriers had lower M/E scores than those carrying the T/T genotype, but the association was not statistically significant. We also analyzed the association between age at onset (AAO) and CLOCK 3111T/C in the bipolar disorder group, and no association was found. Despite the relatively small sample sizes, these results support a possible role of the CLOCK 3111T/C SNP in bipolar disorder. Further studies with larger samples and more polymorphisms are necessary.
authors.affiliation: Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul, Republic of Korea.
authors.forename: Kyu Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Joo Yun
authors.initials: JY
authors.lastname: Song
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Seong Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Joo
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology*; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D056926:CLOCK Proteins