Association of CLOCK, ARNTL, and NPAS2 gene polymorphisms and seasonal variations in mood and behavior

Chronobiol Int. 2015;32(6):785-91. doi: 10.3109/07420528.2015.1049613. Epub 2015 Jul 2.


Seasonal affective disorder (SAD) is a condition of seasonal mood changes characterized by recurrent depression in autumn or winter that spontaneously remits in spring or summer. Evidence has suggested that circadian gene variants contribute to the pathogenesis of SAD. In this study, we investigated polymorphisms in the CLOCK, ARNTL, and NPAS2 genes in relation to seasonal variation in 507 healthy young adults. Seasonal variations were assessed with the Seasonality Pattern Assessment Questionnaire. The prevalence of SAD was 12.0% (winter-type 9.3%, summer-type 2.8%). No significant difference was found between the groups in the genotype distribution of ARNTL rs2278749 and NPAS2 rs2305160. The T allele of CLOCK rs1801260 was significantly more frequent in seasonals (SAD + subsyndromal SAD) compared with non-seasonals (p = 0.020, odds ratio = 1.89, 95% confidence interval = 1.09-3.27). Global seasonality score was significantly different among genotypes of CLOCK rs1801260, but not among genotypes of ARNTL rs2278749 and NPAS2 rs2305160. However, statistical difference was observed in the body weight and appetite subscales among genotypes of ARNTL rs2278749 and in the body weight subscale among genotypes of NPAS2 rs2305160. There was synergistic interaction between CLOCK rs1801260 and ARNTL rs2278749 on seasonality. To our knowledge, this study is the first to reveal an association between the CLOCK gene and seasonal variations in mood and behavior in the Korean population. Although we cannot confirm previous findings of an association between SAD and the ARNTL and NPAS2 genes, these genes may influence seasonal variations through metabolic factors such as body weight and appetite. The interaction of the CLOCK and ARNTL genes contributes to susceptibility for SAD.

Keywords: ARNTL; CLOCK; NPAS2; polymorphism; seasonal affective disorder; seasonality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • Adolescent
  • Adult
  • Affect*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Behavior*
  • CLOCK Proteins / genetics*
  • Circadian Rhythm / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Healthy Volunteers
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Republic of Korea
  • Seasonal Affective Disorder / genetics*
  • Seasons*
  • Young Adult


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • NPAS2 protein, human
  • Nerve Tissue Proteins
  • CLOCK Proteins
  • CLOCK protein, human