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

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 W. Ray, Martin K. Rutter, Richa Saxena
doi: https://doi.org/10.1101/038620
Jacqueline M. Lane
1Center for Human Genetic Research Massachusetts General Hospital, Boston, MA, 02114 USA
2Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
3Broad Institute, Cambridge, MA, 02142 USA
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Irma Vlasac
1Center for Human Genetic Research Massachusetts General Hospital, Boston, MA, 02114 USA
3Broad Institute, Cambridge, MA, 02142 USA
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Simon G. Anderson
4Cardiovascular Research Group, Institute of Cardiovascular Sciences, The University of Manchester, Manchester, M139PL UK
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Simon Kyle
5Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX12JD UK
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William G. Dixon
6Centre for Musculoskeletal Research Institute of Inflammation and Repair, The University of Manchester, Manchester, M139PL UK
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David A. Bechtold
7Faculty of Life Sciences, The University of Manchester, Manchester, M139PL UK
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Shubhroz Gill
3Broad Institute, Cambridge, MA, 02142 USA
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Max A. Little
8Engineering and Applied Science, Aston University, Birmingham, B47ET UK
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Annemarie Luik
5Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX12JD UK
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Andrew Loudon
7Faculty of Life Sciences, The University of Manchester, Manchester, M139PL UK
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Richard Emsley
9Institute of Population Health, The University of Manchester, Manchester, M139PL UK
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Frank AJL. Scheer
10Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, 02115 USA
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Deborah A. Lawlor
11MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS81TH UK
12School of Social and Community Medicine, University of Bristol, Bristol, BS81TH UK
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Susan Redline
10Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, 02115 USA
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David W. Ray
13Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, M139PL UK
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Martin K. Rutter
13Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester, M139PL UK
14Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M139PL UK
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Richa Saxena
1Center for Human Genetic Research Massachusetts General Hospital, Boston, MA, 02114 USA
2Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114 USA
3Broad Institute, Cambridge, MA, 02142 USA
10Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, 02115 USA
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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 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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Posted February 02, 2016.
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Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UKBiobank
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 W. Ray, Martin K. Rutter, Richa Saxena
bioRxiv 038620; doi: https://doi.org/10.1101/038620
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Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UKBiobank
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 W. Ray, Martin K. Rutter, Richa Saxena
bioRxiv 038620; doi: https://doi.org/10.1101/038620

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