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Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UKBiobank

By Jacqueline M Lane, Irma Vlasac, Simon G Anderson, Simon Kyle, William G Dixon, David A Bechtold, Shubhroz Gill, Max A Little, Annemarie Luik, Andrew Loudon, Richard Emsley, Frank AJL Scheer, Deborah A. Lawlor, Susan Redline, David Ray, Martin K Rutter, Richa Saxena

Posted 02 Feb 2016
bioRxiv DOI: 10.1101/038620 (published DOI: 10.1038/ncomms10889)

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 UKBiobank 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.

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