An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output

An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output Sandra P. Smieszek, Jennifer L. Brzezynski, Alyssa R. Kaden, Jordan A. Shinn, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-468649/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version 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. Scientific Communication Health Economics & Outcomes Research sleep-wake patterns cryptochrome circadian clock 1 (CRY1) wild-type (WT) Circadian Metabolic Output Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations Competing interest reported. Conflicts of Interest: 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. Supplementary Files VPVEC1620502ScientificReportsSupplementalv5.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 17 Aug, 2021 Reviews received at journal 16 Jul, 2021 Reviewers agreed at journal 07 Jun, 2021 Reviewers invited by journal 17 May, 2021 Editor assigned by journal 17 May, 2021 Editor invited by journal 06 May, 2021 Submission checks completed at journal 06 May, 2021 First submitted to journal 27 Apr, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-468649","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":25282508,"identity":"13e1ed94-048a-4bca-815e-768a09d9319c","order_by":0,"name":"Sandra P. 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CRY1 lollipop plot showing the variant of interest, rs184039278, with respect to the \ndomains and location of other known coding variants. B. Scatter plot showing delayed sleep period \nin the CRY1 variant group (n = 33) compared to WT controls (n = 34). The x-axis is the bed time \nand the y-axis is the wake time.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1/08d0624d525b1c248ee10ba4.png"},{"id":8910382,"identity":"4c55abce-6885-4546-be8b-183e79bf6b8c","added_by":"auto","created_at":"2021-05-07 13:26:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":504003,"visible":true,"origin":"","legend":"Boxplots showing significant differences in sleep parameters based on data collected \nover a period of 28 days (electronic daily diary) (n = 67). A. Wake Time: mean, pttest= 0.03, pwilcoxon= 0.02 (y-axis is time in hours). B. Midpoint: mean, pttest = 0.05, pwilcoxon = 0.03 (y-axis is time in hours). C. LPS: mean, pttest = 0.01, pwilcoxon = 0.001 (y-axis is time in hours).","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1/c4ab4e900a767a925bd9fd4a.jpg"},{"id":8911474,"identity":"d677b277-6669-4fef-a617-496d662f85c6","added_by":"auto","created_at":"2021-05-07 13:32:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":842966,"visible":true,"origin":"","legend":"Visualization of the sleep diary data for free and work nights for the CRY1 variant group \nand WT controls (n = 67) sorted by bed time.","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1/bb05de2b28420f7735d0bfac.jpg"},{"id":8910953,"identity":"8feaaf86-0bd5-4666-88c1-0d7f7732a679","added_by":"auto","created_at":"2021-05-07 13:29:32","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":371037,"visible":true,"origin":"","legend":"Mean first bowel movement time by genotype (difference of 1 hour and 31 minutes)\nobtained from electronic daily diary (n = 67): mean, pttest = 0.004, pwilcoxon = 0.002 (y-axis is time \nin hours)","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1/271c4d3e201e6f68fc878f56.jpg"},{"id":13629143,"identity":"e1e38bc9-06b8-4c7f-b3dd-b7e2487b2ca3","added_by":"auto","created_at":"2021-09-17 08:04:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":524408,"visible":true,"origin":"","legend":"","description":"","filename":"VPVEC1620502ScientificReportsManuscript5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1_covered.pdf"},{"id":8911738,"identity":"0666232e-38ca-43b0-bf15-cbf9835dcf95","added_by":"auto","created_at":"2021-05-07 13:38:40","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":326530,"visible":true,"origin":"","legend":"","description":"","filename":"VPVEC1620502ScientificReportsManuscript5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1_stamped.pdf"},{"id":8911627,"identity":"0fe3daa5-074d-4adf-8546-74e85f7c4d97","added_by":"auto","created_at":"2021-05-07 13:35:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":911370,"visible":true,"origin":"","legend":"","description":"","filename":"VPVEC1620502ScientificReportsSupplementalv5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-468649/v1/9fd456cc2decadc6642982ec.pdf"}],"financialInterests":"Competing interest reported. Conflicts of Interest: SPS is an employee of Vanda and a stockholder. JLB is an employee of\n16 Vanda and a stockholder. ARK is an employee of Vanda and a stockholder. JAS is an employee\n17 of Vanda and a stockholder. JW is an employee of Vanda and a stockholder. CX is an employee\n18 of Vanda and a stockholder. CP is an employee of Vanda and a stockholder. TÖ is an investigator\n19 for Vanda. MHP is Chief Executive Officer of Vanda.","formattedTitle":"\u003cp\u003eAn Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-468649/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"sleep-wake patterns , cryptochrome circadian clock 1 (CRY1), wild-type (WT), Circadian Metabolic Output","lastPublishedDoi":"10.21203/rs.3.rs-468649/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-468649/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe 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\u0026gt;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.\u003c/p\u003e","manuscriptTitle":"An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-05-07 13:26:30","doi":"10.21203/rs.3.rs-468649/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-08-17T07:34:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-07-17T02:12:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c42a068f-c878-4054-b206-69a7133b8f88","date":"2021-06-07T14:35:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-05-18T00:03:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-05-17T07:44:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-05-06T09:35:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-05-06T04:39:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-04-27T13:11:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bf340569-a127-4b75-94f8-f71f129bb3a2","owner":[],"postedDate":"May 7th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":4155398,"name":"Scientific Communication"},{"id":4155399,"name":"Health Economics \u0026 Outcomes Research"}],"tags":[],"updatedAt":"2021-09-20T03:59:06+00:00","versionOfRecord":[],"versionCreatedAt":"2021-05-07 13:26:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-468649","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-468649","identity":"rs-468649","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}