| Abstract |
Introduction: Sleep is more than a state of no-alertness, since its rhythmicity is genetically programmed and regulated by the circadian mechanism. Polymorphisms in clock genes, which constitute the core of the circadian clock, are associated with many sleep and circadian disorders, as well as individual’s chronotype.
Aims: Aim of this study was to identify rare variants in clock genes and correlate their presence with extreme sleep phenotypes, as identified by actigraphy measurements and subsequently verified by polysomnography.
Methods: In the present study, the exome of 145 participants of the Thalis Cretan Aging Study Cohort (47 cognitively normal controls and 98 patients diagnosed with dementia), was analyzed in order to detect variants in 14 clock genes: CLOCK, BMAL1, NPAS2, PER1, PER2, PER3, CRY1, CRY2, BHLHE40, BHLHE41, NR1D1, REV1, RORA, RORB and one possible regulator of the circadian mechanism, VDR gene. These data were coupled with participants’ actigraphy recordings.
Results: WES analysis identified 57 known and 34 novel clock gene polymorphisms in this cohort. Analysis of the actigraphy measurements in these participants, showed that participants positive for rs2585405 tended to have a short-lasting night Total Sleep Time (night TST; p=0.051), while rs150149747 was also significantly associated with low TST (p=0.046). Both these variants are located in PER1, a crucial regulator of the circadian mechanism. In addition, a PER3 variation, named rs1776342 was also related with decreased TST (p=0.046). Furthermore, 12 rare polymorphisms were identified in participants with extreme actigraphy phenotypes. Interestingly, 6 of these polymorphisms are novel, indicating that many extreme sleep phenotypes could have a genetic basis, which acts as substrate for sleep disorders’ development. For further analysis of participants’ sleep quality, studies in Sleep Medicine Laboratory were performed to evaluate changes in sleep architecture that can be correlated with specific variants.
Conclusions: These preliminary results show that sleep patterns in both cognitively normal controls and patients with dementia could have a strong genetic background.
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Detection of polymorphisms in clock genes in patients with dementia and evaluation of their sleep architecture
