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

TLDR

Being a morning person reflects an individual’s underlying circadian rhythm. We identified 351 loci linked to morningness, showing that individuals with the most morningness alleles sleep 25 min earlier, that these loci enrich circadian, cAMP, glutamate, insulin pathways and brain regions, and that Mendelian randomisation indicates a causal benefit for mental health but no impact on BMI or type 2 diabetes.

Abstract

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.