Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms.
Samuel E JonesJacqueline M LaneAndrew R WoodVincent Theodoor van HeesJessica TyrrellRobin N BeaumontAaron R JeffriesHassan S DashtiMelvyn HillsdonKatherine S RuthMarcus A TukeHanieh YaghootkarSeth A SharpYingjie JieWilliam D ThompsonJames W HarrisonAmy DawesEnda M ByrneHenning TiemeierKarla V AllebrandtJack BowdenDavid W RayRachel M FreathyAnna MurrayDiego R MazzottiPhilip R GehrmanDeborah A LawlorTimothy M FraylingMartin K RutterDavid A HindsRicha SaxenaMichael N WeedonPublished in: Nature communications (2019)
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.
Keyphrases
- genome wide
- genome wide association
- dna methylation
- mental health
- sleep quality
- physical activity
- electronic health record
- copy number
- type diabetes
- big data
- genome wide association study
- body mass index
- atrial fibrillation
- gene expression
- heart rate
- depressive symptoms
- cross sectional
- diabetic retinopathy
- deep learning
- weight loss
- mental illness
- skeletal muscle
- protein kinase