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

• Published in: Nature communications Vol. 10; no. 1; pp. 343 - 11
• Main Authors: Jones, Samuel E., Lane, Jacqueline M., Wood, Andrew R., van Hees, Vincent T., Tyrrell, Jessica, Beaumont, Robin N., Jeffries, Aaron R., Dashti, Hassan S., Hillsdon, Melvyn, Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Sharp, Seth A., Jie, Yingjie, Thompson, William D., Harrison, Jamie W., Dawes, Amy, Byrne, Enda M., Tiemeier, Henning, Allebrandt, Karla V., Bowden, Jack, Ray, David W., Freathy, Rachel M., Murray, Anna, Mazzotti, Diego R., Gehrman, Philip R., Lawlor, Debbie A., Frayling, Timothy M., Rutter, Martin K., Hinds, David A., Saxena, Richa, Weedon, Michael N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/1515; 631/208/205/2138; 631/378/1385/1330; 631/378/1385/519; Adult; Aged; Body mass; Circadian Rhythm; Circadian rhythms; Cyclic AMP - metabolism; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Female; Gene expression; Gene loci; Gene regulation; Genetic Loci; Genome-Wide Association Study; Genomes; Glutamic Acid - metabolism; Health risks; Hindbrain; Humanities and Social Sciences; Humans; Hypothalamus; Insulin; Male; Mental disorders; Mental health; Middle Aged; multidisciplinary; Pituitary; Retina; Science; Science (multidisciplinary); Signal transduction; Sleep; United Kingdom; Whites - genetics; United Kingdom
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-08259-7

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. GWAS have previously found 24 genomic loci associated with chronotype, an individual’s preference for early or late sleep timing. Here, the authors identify 327 additional loci in a sample of 697,828 individuals and further explore the relationships of chronotype with metabolic and psychiatric diseases.