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

Jacqueline M. Lane, Irma Vlasac, Simon G. Anderson, Simon D. Kyle, William G. Dixon, David A. Bechtold, Shubhroz Gill, Max A. Little, Annemarie Luik, Andrew Loudon, Richard Emsley, Frank A. J. L. Scheer, Deborah A. Lawlor, Susan Redline, David W. Ray, Martin K. Rutter and Richa Saxena ()
Additional contact information
Jacqueline M. Lane: Center for Human Genetic Research Massachusetts General Hospital
Irma Vlasac: Center for Human Genetic Research Massachusetts General Hospital
Simon G. Anderson: Cardiovascular Research Group, Institute of Cardiovascular Sciences, The University of Manchester
Simon D. Kyle: Sleep and Circadian Neuroscience Institute (SCNi), University of Oxford
William G. Dixon: Centre for Musculoskeletal Research Institute of Inflammation and Repair, The University of Manchester
David A. Bechtold: Faculty of Life Sciences, The University of Manchester
Shubhroz Gill: Chemical Biology Program, Broad Institute, Cambridge
Max A. Little: Engineering and Applied Science, Aston University
Annemarie Luik: Sleep and Circadian Neuroscience Institute (SCNi), University of Oxford
Andrew Loudon: Faculty of Life Sciences, The University of Manchester
Richard Emsley: Institute of Population Health, The University of Manchester
Frank A. J. L. Scheer: Brigham and Women’s Hospital
Deborah A. Lawlor: MRC Integrative Epidemiology Unit at the University of Bristol
Susan Redline: Brigham and Women’s Hospital
David W. Ray: Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester
Martin K. Rutter: Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester
Richa Saxena: Center for Human Genetic Research Massachusetts General Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10889

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