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Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

dc.contributor.authorJones, SE
dc.contributor.authorLane, JM
dc.contributor.authorWood, AR
dc.contributor.authorvan Hees, VT
dc.contributor.authorTyrrell, J
dc.contributor.authorBeaumont, RN
dc.contributor.authorJeffries, AR
dc.contributor.authorDashti, HS
dc.contributor.authorHillsdon, M
dc.contributor.authorRuth, KS
dc.contributor.authorTuke, MA
dc.contributor.authorYaghootkar, H
dc.contributor.authorSharp, SA
dc.contributor.authorJie, Y
dc.contributor.authorThompson, WD
dc.contributor.authorHarrison, JW
dc.contributor.authorDawes, A
dc.contributor.authorByrne, EM
dc.contributor.authorTiemeier, H
dc.contributor.authorAllebrandt, KV
dc.contributor.authorBowden, J
dc.contributor.authorRay, DW
dc.contributor.authorFreathy, RM
dc.contributor.authorMurray, A
dc.contributor.authorMazzotti, DR
dc.contributor.authorGehrman, PR
dc.contributor.authorLawlor, DA
dc.contributor.authorFrayling, TM
dc.contributor.authorRutter, MK
dc.contributor.authorHinds, DA
dc.contributor.authorSaxena, R
dc.contributor.authorWeedon, MN
dc.date.accessioned2019-01-31T15:11:19Z
dc.date.issued2019-01-29
dc.description.abstractBeing a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipEuropean Research Councilen_GB
dc.description.sponsorshipRoyal Societyen_GB
dc.description.sponsorshipDiabetes Research and Wellness Foundationen_GB
dc.description.sponsorshipEuropean Union Seventh Framework Programme (FP7/2007–2013)en_GB
dc.description.sponsorshipNational Institutes of Health (NIH)en_GB
dc.description.sponsorshipUniversity of Manchesteren_GB
dc.description.sponsorshipNational Health and Medical Research Council of Australiaen_GB
dc.description.sponsorshipMGH Research Scholar Funden_GB
dc.description.sponsorshipDutch Medical Research Foundation grantsen_GB
dc.identifier.citationVol. 10, article 343en_GB
dc.identifier.doi10.1038/s41467-018-08259-7
dc.identifier.grantnumberMR/M005070/1en_GB
dc.identifier.grantnumberWT097835MFen_GB
dc.identifier.grantnumberSZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERCen_GB
dc.identifier.grantnumber323195en_GB
dc.identifier.grantnumber104150/Z/14/Zen_GB
dc.identifier.grantnumber104150/Z/14/Zen_GB
dc.identifier.grantnumber669545en_GB
dc.identifier.grantnumber107849/Z/15/Zen_GB
dc.identifier.grantnumberF32DK102323en_GB
dc.identifier.grantnumber4T32HL007901en_GB
dc.identifier.grantnumber1145645en_GB
dc.identifier.grantnumber1078901en_GB
dc.identifier.grantnumber1087889en_GB
dc.identifier.grantnumberNIH R01DK107859en_GB
dc.identifier.grantnumberNIH R01DK102696en_GB
dc.identifier.grantnumber016.VICI.170.200en_GB
dc.identifier.grantnumberVIDI 017.106.370en_GB
dc.identifier.urihttp://hdl.handle.net/10871/35688
dc.language.isoenen_GB
dc.publisherNature Researchen_GB
dc.rights© 2019 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_GB
dc.titleGenome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythmsen_GB
dc.typeArticleen_GB
dc.date.available2019-01-31T15:11:19Z
dc.identifier.issn2041-1723
dc.descriptionThis is the final version. Available on open access from Nature Research via the DOI in this recorden_GB
dc.descriptionData availability: Summary statistics for the top 10,000 chronotype meta-analysis variants are provided in Supplementary Data 10. The full set of UK Biobank-only chronotype and morning person GWAS summary statistics can be found at http://www.t2diabetesgenes.org/data/ and on the Sleep Disorder Knowledge Portal at http://sleepdisordergenetics.org/informational/data/. Full meta-analysis summary statistics can be requested directly from 23andMe Inc. (see https://research.23andme.com/collaborate/#publication). The GGIR R script used to generate the activity monitor measures (Supplementary Data 14) is available with the online version of this article.en_GB
dc.identifier.journalNature Communicationsen_GB
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2018-12-19
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2019-01-29
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2019-01-31T13:02:54Z
refterms.versionFCDAM
refterms.dateFOA2019-01-31T15:11:25Z
refterms.panelAen_GB


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© 2019 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's licence is described as © 2019 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.