CLOCK Genetic Variations Are Associated with Age-related Changes in Sleep Duration and Brain Volume

By Prof. Hyang Woon Lee
Department of Neurology
PURE Research Profile
leeh@ewha.ac.kr

Sleep and/or circadian dysfunction have been reported to have close links with aging. Sleep dysfunction including short sleep duration and disturbed sleep–wake cycles could be an early pathologic hallmark of multiple neurodegenerative conditions. However, this link be¬tween sleep and cognition does not necessarily occur only in association with neurodegenerative processes, but can also be observed in otherwise healthy individuals aging normally. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, Circadian Locomotor Output Cycles Kaput (CLOCK), has been linked to both aging-related sleep disturbances and neurodegenerative diseases.

Total 2,221 middle-aged and older participants dem¬onstrate the association of CLOCK genetic variations with sleep duration changes and lower cortical volumes in distinct brain areas. We examined haplotypes consisting of a combination of 5 CLOCK gene SNPs that were significantly associated with sleep duration changes (rs10002541, rs6850524, rs4580704, rs3805151, rs3749474). The specific haplotype (CGTCT) associates with decreases in sleep duration over time as well as lower total brain tissue and gray matter volume, especially in frontal and temporal regions of the left hemisphere. In addition, CGTCT haplotype parti¬cipants with decreased sleep duration over time showed lower brain volumes in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere.

Of note, CLOCK genetic variations could contribute to change in sleep duration over time and alteration of brain cortical volumes. Ultimately, that circadian genetic factors play a role in interindividual variability in longitudinal sleep duration change and brain cortical volumes.

* Related Article
S.E. Kim, S. Kim, H.J. Kim, R.E.Y. Kim, S.A. Kim, C. Shin, H.W. Lee*, CLOCK genetic variations are associated with age-related changes in sleep duration and brain volume. Journal of Gerontology, Medical Sciences, doi.org/10.1093/gerona/glab365 (2021).