Tohoku J. Exp. Med., 2021 November, 255(4)

Circadian Clock Gene Polymorphisms and Sleep-Onset Problems in a Population-Based Cohort Study: The Yamagata Study

Kaori Sakurada,1 Tsuneo Konta,2 Sanae Takahashi,3 Narumi Murakami,1 Hidenori Sato,4 Ryoko Murakami,4 Masafumi Watanabe,4 Kenichi Ishizawa,4 Yoshiyuki Ueno,4 Hidetoshi Yamashita4 and Takamasa Kayama4

1Department of Fundamental Nursing, Yamagata University Graduate School of Nursing, Yamagata, Yamagata, Japan
2Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Yamagata, Yamagata, Japan
3Division of Nursing, Yamagata University Hospital, Yamagata, Yamagata, Japan
4Global Center of Excellence, Yamagata University School of Medicine, Yamagata, Yamagata, Japan

A number of genome-wide association studies have investigated sleep phenotypes and disorders in humans. However, the contribution of genetic variation to sleep problems in Japanese populations has remained unclear. Sleep-onset problems are the most common symptom of insomnia. Here, we examined the relationship between single nucleotide polymorphisms (SNPs) of BMAL1 (ARNTL1), CLOCK, CRY1, CRY2, and PER2, which are genes involved in the clock mechanism, and sleep-onset problems in a Japanese general population. This study included 1,397 subjects aged ≥ 40 years who participated in an annual health check-up in Yamagata Prefecture. A total of 80 SNPs of 5 circadian clock genes were analyzed. Multivariate logistic regression analyses identified variant rs11113179 in CRY1 and variants rs1026071 and rs1562438 in BMAL1 as genetic risk factors for sleep induction disorder. These findings suggest that CRY1 and BMAL1 polymorphisms are related to sleep-onset problems in a Japanese general population. However, none of the SNPs remained significant at a stringent level of multiple correction.

Keywords —— circadian clock gene; Japanese general population; single nucleotide polymorphism; sleep-onset problems; Yamagata study


Tohoku J. Exp. Med 2021, 255, 325-331.

Correspondence: Kaori Sakurada, Department of Fundamental Nursing, Yamagata University Graduate School of Nursing, 2-2-2 Iidanishi, Yamagata, Yamagata 990-9585, Japan.