title: Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank.
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.
authors.affiliation: Center for Human Genetic Research Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lane
authors.affiliation: Center for Human Genetic Research Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: Irma
authors.initials: I
authors.lastname: Vlasac
authors.affiliation: Cardiovascular Research Group, Institute of Cardiovascular Sciences, The University of Manchester, Manchester M139PL, UK.
authors.forename: Simon G
authors.identifier: http://orcid.org/0000-0002-8896-073X
authors.initials: SG
authors.lastname: Anderson
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX12JD, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Kyle
authors.affiliation: Centre for Musculoskeletal Research Institute of Inflammation and Repair, The University of Manchester, Manchester M139PL, UK.
authors.forename: William G
authors.identifier: http://orcid.org/0000-0001-5881-4857
authors.initials: WG
authors.lastname: Dixon
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M139PL, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Bechtold
authors.affiliation: Chemical Biology Program, Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: Shubhroz
authors.initials: S
authors.lastname: Gill
authors.affiliation: Department of Mathematics, Engineering and Applied Science, Aston University, Birmingham B47ET, UK.
authors.forename: Max A
authors.initials: MA
authors.lastname: Little
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX12JD, UK.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Luik
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M139PL, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Loudon
authors.affiliation: Institute of Population Health, The University of Manchester, Manchester M139PL, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Emsley
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.|Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol BS81TH, UK.|School of Social and Community Medicine, University of Bristol, Bristol BS81TH, UK.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.|Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester M139PL, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Ray
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester M139PL, UK.|Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M139PL, UK.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Rutter
authors.affiliation: Center for Human Genetic Research Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA.|Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D006113:United Kingdom; D044465:White People / Q000235:genetics*