Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank
Lane JM., Vlasac I., Anderson SG., Kyle SD., Dixon WG., Bechtold DA., Gill S., Little MA., Luik A., Loudon A., Emsley R., Scheer FAJL., Lawlor DA., Redline S., Ray DW., Rutter MK., Saxena R.
Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.