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

Jones, S. E.; Lane, J. M.; Wood, A. R.; van Hees, V. T.; Tyrrell, J.; Beaumont, R. N.; Jeffries, A. R.; Dashti, H. S.; Hillsdon, M.; Ruth, K. S.; Tuke, M. A.; Yagohootkar, H.; Sharp, S. A.; Ji, Y.; Harrison, J. W.; Dawes, A.; Byrne, E. M.; Tiemeier, H.; Allebrandt, K. V.; Bowden, J.; Ray, D. W.; Freathy, R. M.; Murray, A.; Mazzotti, D. R.; Gehrman, P. R.; 23andMe Research Team,; Lawlor, D. A.; Frayling, T. M.; Rutter, M. K.; Hinds, D. A.; Saxena, R.; Weedon, M. N.

doi:10.1101/303941

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bioRxiv · 10.1101/303941

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

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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 persons 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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Jones, S. E., Lane, J. M., Wood, A. R., van Hees, V. T., Tyrrell, J., Beaumont, R. N., Jeffries, A. R., Dashti, H. S., Hillsdon, M., Ruth, K. S., Tuke, M. A., Yagohootkar, H., Sharp, S. A., Ji, Y., Harrison, J. W., Dawes, A., Byrne, E. M., Tiemeier, H., Allebrandt, K. V., Bowden, J., Ray, D. W., Freathy, R. M., Murray, A., Mazzotti, D. R., Gehrman, P. R., 23andMe Research Team,, Lawlor, D. A., Frayling, T. M., Rutter, M. K., Hinds, D. A., Saxena, R., Weedon, M. N.. 2018-04-19. Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease. https://doi.org/10.1101/303941

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