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,
Hassan S Dashti,
Katherine S. Ruth,
Marcus A. Tuke,
William D Thompson,
Jamie W. Harrison,
Enda M. Byrne,
Karla V. Allebrandt,
David W. Ray,
Diego R. Mazzotti,
Philip R. Gehrman,
the 23andMe Research Team,
Martin K Rutter,
David A. Hinds,
Posted 19 Apr 2018
bioRxiv DOI: 10.1101/303941
Posted 19 Apr 2018
Using data from 697,828 research participants from 23andMe and UK Biobank, we identified 351 loci associated with being a morning person, a behavioural indicator of a person's underlying circadian rhythm. These loci were validated in 85,760 individuals with activity-monitor derived measures of sleep timing: the mean sleep timing of the 5% of individuals carrying the most "morningness" alleles was 25.1 minutes (95% CI: 22.5, 27.6) earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian rhythm and insulin pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary (all FDR<1%). We provide some evidence that being a morning person was causally associated with reduced risk of schizophrenia (OR: 0.89; 95% CI: 0.82, 0.96), depression (OR: 0.94; 95% CI: 0.91, 0.98) and a lower age at last childbirth in women (β: -0.046 years; 95% CI: -0.067, -0.025), but was not associated with BMI (β: -4.6x10-4; 95% CI: -0.044, 0.043) or type 2 diabetes (OR: 1.00; 95% CI: 0.91, 1.1). This study offers new insights into the biology of circadian rhythms and disease links in humans.
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