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Abstract
The clock gene (CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study. As for function, rs1801260 has been speculated to affect mRNA. Therefore, the authors investigated the association between the three tagging single-nucleotide polymorphisms (SNPs) (rs3736544, rs1801260, and rs3749474) in CLOCK and risk of BP (n = 867) and MDD (n = 139) compared to controls (n = 889) in the Japanese population. In addition, we also performed an updated meta-analysis of nine published, genetic association studies investigating the relationship between rs1801260 and mood disorder risk, comprising 3321 mood disorders cases and 3574 controls. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global pBP = .605 and global pMDD = .211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders. (Author correspondence: [email protected])
ACKNOWLEDGMENTS
This work was supported in part by research grants from the Japan Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation). Dr. Kishi is a postdoctoral fellow for research abroad, and is additionally supported by the Japan Research Foundation for Clinical Pharmacology and the Ministry of Education.
The authors thank Dr. Hader Mansour, Dr. Vishwajit Nimgaonkar, and Dr. Mònica Gratacòs for providing genotype information for the study. The authors also thank Ms. M. Miyata and Ms. S. Ishihara for their technical support.
Declaration of interest: Dr. Correll has been a consultant and/or advisor to or has received honoraria from Actelion, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, IntraCellular Therapies, Ortho-McNeill/Janssen/J&J, Merck, Novartis, Otsuka, Pfizer, and Sepracor/Sunovion. He has received grant support from the Feinstein Institute for Medical Research, the National Institute of Mental Health (NIMH), the National Alliance for Research in Schizophrenia and Depression (NARSAD), and Ortho-McNeill/Janssen/J&J. Dr. Correll declares that he has no direct conflict of interest or grant support that is directly related to the content of the study. However, as any potential conflict arising from the relationships with companies or grant agencies cannot fully be ruled out, he followed the full transparency rule, listing all such relationships that took place in the past 12 months.