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

Research output: Contribution to journalArticle

  • Samuel E. Jones
  • Jacqueline M. Lane
  • Andrew R. Wood
  • Vincent T. van Hees
  • Jessica Tyrrell
  • Robin N. Beaumont
  • Aaron R. Jeffries
  • Hassan S. Dashti
  • Melvyn Hillsdon
  • Katherine S. Ruth
  • Marcus A. Tuke
  • Hanieh Yaghootkar
  • Seth A. 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
  • Debbie A. Lawlorhttp://orcid.org/0000-0002-6793-2262
  • Timothy M. Frayling
  • Martin K. Rutter
  • David A. Hinds
  • Richa Saxena
  • Michael N. Weedon
Original languageEnglish
Article number343
Number of pages11
JournalNature Communications
Volume10
Issue number1
DOIs
DateAccepted/In press - 19 Dec 2018
DatePublished (current) - 31 Jan 2019

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.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Nature at https://doi.org/10.1038/s41467-018-08259-7 . Please refer to any applicable terms of use of the publisher.

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