Research Papers: Gerotarget (Focus on Aging):

Effects of circadian clock genes and environmental factors on cognitive aging in old adults in a Taiwanese population

Eugene Lin _, Po-Hsiu Kuo, Yu-Li Liu, Albert C. Yang, Chung-Feng Kao and Shih-Jen Tsai

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Oncotarget. 2017; 8:24088-24098. https://doi.org/10.18632/oncotarget.15493

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Eugene Lin1,2,3, Po-Hsiu Kuo4, Yu-Li Liu5, Albert C. Yang6,7, Chung-Feng Kao8 and Shih-Jen Tsai6,7

1 Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

2 Vita Genomics, Inc., Taipei, Taiwan

3 TickleFish Systems Corporation, Seattle, WA, USA

4 Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan

5 Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan

6 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

7 Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan

8 Department of Agronomy, College of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan

Correspondence to:

Eugene Lin, email:

Shih-Jen Tsai, email:

Keywords: circadian clock genes; circadian rhythms; cognitive aging; gene-gene and gene-environment interactions; single nucleotide polymorphisms; Gerotarget

Received: September 20, 2016 Accepted: February 06, 2017 Published: February 16, 2017


Previous animal studies have indicated associations between circadian clock genes and cognitive impairment . In this study, we assessed whether 11 circadian clockgenes are associated with cognitive aging independently and/or through complex interactions in an old Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to evaluate cognitive function. Our data showed associations between cognitive aging and single nucleotide polymorphisms (SNPs) in 4 key circadian clock genes, CLOCK rs3749473 (p = 0.0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and RORB rs10781247 (p = 7.9 x 10-5). We also found that interactions between CLOCK rs3749473, NPAS2 rs17655330, RORA rs13329238, and RORB rs10781247 affected cognitive aging (p = 0.007). Finally, we investigated the influence of interactions between CLOCK rs3749473, RORA rs13329238, and RORB rs10781247 with environmental factors such as alcohol consumption, smoking status, physical activity, and social support on cognitive aging (p = 0.002 ~ 0.01). Our study indicates that circadian clock genes such as the CLOCK, NPAS2, RORA, and RORB genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-environment interactions.

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