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

Hae In Kim, Heon Jeong Lee, Chul Hyun Cho, Seung Gul Kang, Ho Kyoung Yoon, Young Min Park, Seung Hwan Lee, Joung Ho Moon, Hye Min Song, Eunil Lee, Leen Kim

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38 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalChronobiology International
Issue number6
Publication statusPublished - 2015 Jul 1

Bibliographical note

Funding Information:
The authors have no conflicts of interest to declare. This study was supported by the Future Environmental R&D grant funded by the Korea Environmental Industry and Technology Institute (No. RE201206020) and by the Korea Health 21 R&D Project funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3212).

Publisher Copyright:
© 2015 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.


  • NPAS2
  • Polymorphism
  • Seasonal affective disorder
  • Seasonality

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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