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Observational Study
.2021 Oct 11;11(1):20103.
doi: 10.1038/s41598-021-99418-2.

An observational study investigating the CRY1Δ11 variant associated with delayed sleep-wake patterns and circadian metabolic output

Affiliations
Observational Study

An observational study investigating the CRY1Δ11 variant associated with delayed sleep-wake patterns and circadian metabolic output

Sandra P Smieszek et al. Sci Rep..

Abstract

We conducted an observational research study to collect information on sleep-wake patterns from participants with a confirmed status of the cryptochrome circadian clock 1 (CRY1) splicing variant, CRY1Δ11 c.1657 + 3A > C, and their controls, defined as wild-type (WT) family members. Altogether, 67 participants were enrolled and completed this study in Turkey, recruited from a list of families with at least one CRY1-confirmed member. We measured sleep-wake patterns and metabolic output, specifically time and frequency of bowel movements, for all participants by daily post-sleep diaries over 28 days. The sleep diary measured self-reported bed time, wake time, midpoint of sleep, and latency to persistent sleep (LPS), and accounted for naps and awakenings for religious purposes. Wake time and midpoint of sleep were significantly later in the CRY1Δ11 variant group versus WT, and LPS was significantly greater in participants in the CRY1Δ11 variant group. The mean bed time on all nights of sleep was later in participants with a CRY1Δ11 variant versus WT. Additionally, participants with a CRY1Δ11 variant had significantly affected metabolic outputs, measured by later bowel movements than WT participants. These results demonstrate that, on average, individuals with the studied splicing variant experience pronounced delays in sleep period and circadian-related metabolic processes.

© 2021. The Author(s).

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Conflict of interest statement

SPS is an employee of Vanda and a stockholder. JLB is an employee of 16 Vanda and a stockholder. ARK is an employee of Vanda and a stockholder. JAS is an employee 17 of Vanda and a stockholder. JW is an employee of Vanda and a stockholder. CX is an employee 18 of Vanda and a stockholder. CP is an employee of Vanda and a stockholder. TÖ is an investigator 19 for Vanda. MHP is Chief Executive Officer of Vanda.

Figures

Figure 1
Figure 1
A.CRY1 lollipop plot showing the variant of interest, rs184039278, with respect to the domains and location of other known coding variants.
Figure 2
Figure 2
Boxplots showing significant differences in sleep parameters based on data collected over a period of 28 days (electronic daily diary) for CRY1Δ11 variant group (n = 33) compared to WT controls (n = 34). A. Wake Time pwilcoxon = 0.02 (y-axis is time in hours). B. Midpoint pwilcoxon = 0.03 (y-axis is time in hours). C. LPS pwilcoxon = 0.001 (y-axis is time in hours).
Figure 3
Figure 3
Visualization of the sleep diary data for free night (without obligation on the next day) and work nights (necessity to work in the morning) for the CRY1Δ11 variant group (n = 33) compared to WT controls (n = 34) sorted by bed time.
Figure 4
Figure 4
Mean first bowel movement time by genotype (difference of 1 h and 31 min) obtained from electronic daily diary for CRY1Δ11 variant group (n = 33) and WT controls (n = 34) pwilcoxon = 0.002 (y-axis is time in hours).
See this image and copyright information in PMC

References

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    1. Karczewski, K.J., et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes.bioRxiv. August 531210 (2019). 10.1101/531210

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