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Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease

View ORCID ProfileSamuel E. Jones, View ORCID ProfileJacqueline M. Lane, View ORCID ProfileAndrew R. Wood, View ORCID ProfileVincent T. van Hees, View ORCID ProfileJessica Tyrrell, View ORCID ProfileRobin N. Beaumont, View ORCID ProfileAaron Jefferies, View ORCID ProfileHassan S. Dashti, View ORCID ProfileMelvyn Hillsdon, View ORCID ProfileKatherine S. Ruth, View ORCID ProfileMarcus A. Tuke, Hanieh Yaghootkar, View ORCID ProfileSeth Sharp, Yingjie Jie, William D. Thompson, View ORCID ProfileJamie W. Harrison, Amy Dawes, View ORCID ProfileEnda M. Byrne, View ORCID ProfileHenning Tiemeier, View ORCID ProfileKarla V. Allebrandt, View ORCID ProfileJack Bowden, View ORCID ProfileDavid W. Ray, View ORCID ProfileRachel M. Freathy, View ORCID ProfileAnna Murray, View ORCID ProfileDiego R. Mazzotti, View ORCID ProfilePhilip R. Gehrman, the 23andMe Research Team, View ORCID ProfileDebbie A. Lawlor, View ORCID ProfileTimothy M. Frayling, View ORCID ProfileMartin K. Rutter, View ORCID ProfileDavid Hinds, View ORCID ProfileRicha Saxena, View ORCID ProfileMichael N. Weedon
doi: https://doi.org/10.1101/303941
Samuel E. Jones
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Jacqueline M. Lane
2Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
3Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
4Broad Institute, Cambridge, MA, USA
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Andrew R. Wood
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Vincent T. van Hees
5Netherlands eScience Center, Amsterdam, The Netherlands
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Jessica Tyrrell
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Robin N. Beaumont
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Aaron Jefferies
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Hassan S. Dashti
2Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
4Broad Institute, Cambridge, MA, USA
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Melvyn Hillsdon
6Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK
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Katherine S. Ruth
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Marcus A. Tuke
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Hanieh Yaghootkar
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Seth Sharp
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Yingjie Jie
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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William D. Thompson
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Jamie W. Harrison
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Amy Dawes
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Enda M. Byrne
7The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia
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Henning Tiemeier
8Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands
9Department of Psychiatry, Erasmus Medical Center, Rotterdam, Netherlands
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Karla V. Allebrandt
10Department of Translational Informatics, Translational Medicine Early Development, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany
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Jack Bowden
11MRC Integrative Epidemiology Unit at the University of Bristol, UK
12Population Health Sciences, Bristol Medical School, University of Bristol, UK
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David W. Ray
13Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
14Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
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Rachel M. Freathy
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Anna Murray
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Diego R. Mazzotti
15Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, United States
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Philip R. Gehrman
16Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
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1723 and Me Inc., 899 W. Evelyn Avenue, Mountain View, California 94041, USA
Debbie A. Lawlor
11MRC Integrative Epidemiology Unit at the University of Bristol, UK
12Population Health Sciences, Bristol Medical School, University of Bristol, UK
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Timothy M. Frayling
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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Martin K. Rutter
13Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
14Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK
18Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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David Hinds
1723 and Me Inc., 899 W. Evelyn Avenue, Mountain View, California 94041, USA
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Richa Saxena
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
2Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
3Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
19Departments of Medicine, Brigham and Women’s Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston
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Michael N. Weedon
1Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
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  • ORCID record for Michael N. Weedon
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Abstract

Using genome-wide data from 697,828 research participants from 23andMe and UK Biobank, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a person’s underlying circadian rhythm, from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we show that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of individuals carrying the most “morningness” alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. We provide evidence that being a morning person is causally associated with better mental health but does not appear to affect BMI or Type 2 diabetes. This study offers new insights into the biology of circadian rhythms and links to disease in humans.

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Posted September 13, 2018.
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Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease
Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. van Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron Jefferies, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. Allebrandt, Jack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, the 23andMe Research Team, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David Hinds, Richa Saxena, Michael N. Weedon
bioRxiv 303941; doi: https://doi.org/10.1101/303941
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Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease
Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. van Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron Jefferies, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. Allebrandt, Jack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, the 23andMe Research Team, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David Hinds, Richa Saxena, Michael N. Weedon
bioRxiv 303941; doi: https://doi.org/10.1101/303941

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