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 person's 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.
Footnotes
In this revision, we have attempted to provide more biological interpretation through additional finemapping, annotation and eQTL analyses, and through more in-depth discussions of results already present in the paper. Through these additional analyses (the results of which are presented in additional supplementary tables), we highlight potential molecular mechanisms (and possible therapeutic targets) for influencing chronotype. We have simplified the MR section by testing only phenotypes with sufficient evidence of genetic overlap and have discussed the causal association between chronotype and schizophrenia. For the MR results highlighted in the paper, we have moved what were supplementary figures to actual figures in the manuscript.
