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

Author

Listed:
  • Samuel E. Jones

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Jacqueline M. Lane

    (Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School
    Broad Institute)

  • Andrew R. Wood

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Vincent T. Hees

    (Netherlands eScience Center)

  • Jessica Tyrrell

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Robin N. Beaumont

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Aaron R. Jeffries

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Hassan S. Dashti

    (Massachusetts General Hospital
    Broad Institute)

  • Melvyn Hillsdon

    (University of Exeter)

  • Katherine S. Ruth

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Marcus A. Tuke

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Hanieh Yaghootkar

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Seth A. Sharp

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Yingjie Jie

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • William D. Thompson

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Jamie W. Harrison

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Amy Dawes

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Enda M. Byrne

    (Institute for Molecular Bioscience)

  • Henning Tiemeier

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Karla V. Allebrandt

    (Industriepark Höchst)

  • Jack Bowden

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • David W. Ray

    (University of Manchester
    University of Manchester)

  • Rachel M. Freathy

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Anna Murray

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Diego R. Mazzotti

    (University of Pennsylvania)

  • Philip R. Gehrman

    (Perelman School of Medicine of the University of Pennsylvania)

  • Debbie A. Lawlor

    (MRC Integrative Epidemiology Unit at the University of Bristol
    University of Bristol)

  • Timothy M. Frayling

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

  • Martin K. Rutter

    (University of Manchester
    University of Manchester
    Manchester Academic Health Science Centre)

  • David A. Hinds

    (23andMe Inc.)

  • Richa Saxena

    (Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School
    Harvard Medical School)

  • Michael N. Weedon

    (University of Exeter Medical School, Royal Devon & Exeter Hospital)

Abstract

Being 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.

Suggested Citation

  • Samuel E. Jones & Jacqueline M. Lane & Andrew R. Wood & Vincent T. Hees & Jessica Tyrrell & Robin N. Beaumont & Aaron R. Jeffries & Hassan S. Dashti & Melvyn Hillsdon & Katherine S. Ruth & Marcus A. T, 2019. "Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08259-7
    DOI: 10.1038/s41467-018-08259-7
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    Cited by:

    1. Matthew C. Pahl & Claudia A. Doege & Kenyaita M. Hodge & Sheridan H. Littleton & Michelle E. Leonard & Sumei Lu & Rick Rausch & James A. Pippin & Maria Caterina Rosa & Alisha Basak & Jonathan P. Bradf, 2021. "Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Maria Niarchou & Daniel E. Gustavson & J. Fah Sathirapongsasuti & Manuel Anglada-Tort & Else Eising & Eamonn Bell & Evonne McArthur & Peter Straub & J. Devin McAuley & John A. Capra & Fredrik Ullén & , 2022. "Genome-wide association study of musical beat synchronization demonstrates high polygenicity," Nature Human Behaviour, Nature, vol. 6(9), pages 1292-1309, September.

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